bims-ribost Biomed News
on Ribostasis and translation stress
Issue of 2026–03–08
forty papers selected by
Cédric Chaveroux, CNRS
  1. GCN2 in proteostasis: structural logic, signalling networks and disease.
  2. Mapping the RNA methylome under drought: techniques, mechanisms, and agricultural implications.
  3. Mapping the temporality and structural impacts of modifications in E. coli tRNAs.
  4. MondoA mediates transcriptional coordination between the MYC network and the integrated stress response in pancreatic cancer.
  5. The related EIF4G3 and EIF4G4 initiation factors from Leishmania: dissimilar modes of action during translation revealed by a comparative proteomic approach.
  6. Strategies to Improve the Stability and Translation of Therapeutic mRNAs.
  7. PELOTA at the Crossroads of Ribosome-associated quality control and Silencing: Coordinating Development, Stress, and Immunity in Plants.
  8. Mapping the inter- and intra-genic codon-usage landscape in Homo sapiens.
  9. The expanding role of m6A RNA modification in plant-virus dynamics: friend, foe, or both?
  10. Nucleolus as a cornerstone linking proliferation and metabolism to cellular responses to stress: involvement of transcription factors MYC and p53.
  11. RNA-specific local translation is patterned by condensates for multinucleate cell growth.
  12. Coevolution of RNase P and the ribosome.
  13. N6-Methylation Modification: Its Role in Regulating Cell Senescence and Inflammation in Osteoarthritis and Intervertebral Disc Degeneration.
  14. Plant P-Bodies in Post-Transcriptional Control: Composition, Dynamics, and Context-Dependent Roles.
  15. Regulatory links between the circadian clock and stress-induced biomolecular condensates.
  16. METTL3-mediated N6-methyladenosine modification of Dnajb1 modulates cardiomyocyte ferroptosis during myocardial infarction.
  17. METTL3-Mediated m6A Regulation of CircINTS4/miR-146b-3p Axis in Rheumatoid Arthritis.
  18. Oncogenic KRAS Rewires Stress Granule Dynamics: Mechanisms and Therapeutic Opportunities.
  19. The Yin-Yang of Stress and Senescence: Integrated Stress Response and SASP Crosstalk in Stem Cell Fate, Regeneration, and Disease.
  20. Emerging roles of RNA N5-methylcytosine modification in reproductive physiology and gynecological diseases.
  21. The UTRs of Leishmania donovani vary in length and are enriched in potential regulatory structures.
  22. Small-Molecule Activation of mRNA Translation by Click-to-Release Reaction in Cells.
  23. Light-induced m6A RNA modification regulates anthocyanin accumulation during rose petal coloration.
  24. FUS is an N1- and N6-methyladenosine-binding protein.
  25. RNA therapeutics 2.0: Expanding the landscape from mRNA vaccines to splicing modulators and beyond.
  26. METTL3 promotes prostate cancer cell metastasis and EMT by mediating NUP210 m6A modification.
  27. Active Site Assembly by SMG5 as a Mechanism for SMG6 Endonuclease Licencing in Nonsense-mediated mRNA Decay.
  28. Metabolism of Epigenetic Ribonucleosides Leads to Nucleolar Stress and Cytotoxicity.
  29. The emerging role of m6A methylation in prostate-related diseases: mechanisms and clinical implications.
  30. Immune activation reprograms growth mRNA stability to shape plant growth-defense trade-offs.
  31. Decoding the role of RPL38 in lung adenocarcinoma: a multi-omics approach.
  32. EpCAM silencing suppresses aggressive phenotypes and induces partial redifferentiation in anaplastic thyroid cancer cells.
  33. Structural and mechanistic basis of mTORC2 activation of protein kinase AKT/PKB.
  34. Long non‑coding RNA NKILA regulates the JAK2/STAT3 pathway to exacerbate TGF‑β1‑mediated renal fibrosis.
  35. RPL28 mediates sorafenib resistance in hepatocellular carcinoma by downregulating CDC6 expression.
  36. Granules Gone Rogue: Nuclear and Cytoplasmic Ribonucleoprotein Structures in Amyotrophic Lateral Sclerosis-Fused in Sarcoma (ALS-FUS) Pathology.
  37. NPM1 Drives ERK1/2-dependent Tumor Progression in Lung Cancer.
  38. Loss of Splicing Homeostasis as a Hallmark of Aging.
  39. 5PSeq explorer: interactive analysis of Co-translational mRNA decay and ribosome dynamics.
  40. The role of ubiquitination in regulating secondary metabolism in plants: mechanistic insights and biological significance.
  1. FEBS J. 2026 Mar 04.
    GCN2 in proteostasis: structural logic, signalling networks and disease.
    JiaYi Zhu, Stefan J Marciniak.
      Proteostasis is the finely tuned balance of protein synthesis, folding and degradation essential for cellular health. When this equilibrium is disrupted, misfolded proteins accumulate, triggering adaptive stress responses such as the unfolded protein response and the integrated stress response (ISR). Central to the ISR is the kinase GCN2, a sensor of amino acid deprivation and ribosomal stress. Upon activation, GCN2 phosphorylates eIF2α, dampening global translation while selectively enhancing the synthesis of the stress-responsive transcription factors ATF4 and CHOP. ATF4 orchestrates a broad transcriptional programme that supports amino acid metabolism, redox homeostasis, autophagy and proteasomal degradation, which are key processes for restoring proteostasis. Beyond its canonical role, GCN2 interfaces with other regulatory networks modulating mTORC1 to promote autophagic clearance of damaged proteins and organelles, facilitating stress granule formation, and integrating signals from oxidative and endoplasmic reticulum stress to rebalance the proteome. Dysregulated GCN2 activity has been implicated in diverse pathologies including neurodegeneration, cancer and pulmonary vascular disease, positioning it as a promising therapeutic target. In this review, we explore how GCN2 links nutrient sensing to translational control and metabolic adaptation, and how its central role in proteostasis may inform new strategies for treating diseases driven by protein misfolding and stress pathway imbalance.
    Keywords:  GCN2; amino acid sensing; integrated stress response; proteostasis; translational control
    DOI:  https://doi.org/10.1111/febs.70480
  2. Front Plant Sci. 2026 ;17 1766123
    Mapping the RNA methylome under drought: techniques, mechanisms, and agricultural implications.
    Xiaoru Fan, Yong Zhang.
      Drought stress is one of the most devastating threats to global agriculture. Understanding plant adaptation to water scarcity is of paramount importance for food security. In the last several years, epigenetic regulation, especially RNA methylation, has been shown to play an important role in post-transcriptional gene regulation in plant stress response. Here, we summarize recent advances in studying the epitranscriptomic mechanisms underlying plant drought tolerance. We will introduce various types of RNA modifications, provide an overview of "writer", "eraser" and "reader" proteins mediating m6A modification in plant system, and discuss different technologies for detecting m6A and several other modifications including m5C, m1A, m3C, m7G and m1A with focus on principles and technical consideration. Finally, we will discuss evidence from multiple species to suggest that water deficiency can alter the abundance of m6A modification on RNA molecules in a dynamic manner. The modified transcripts go through differential stability, translation efficiency and process proficiency levels to regulate various physiological processes including but not limited to stomatal movement, ROS signaling and hormonal action. Furthermore, we will also highlight the possible means through which modulation of m6A level could be utilized for generating drought tolerant crops through genetic or biotechnological approaches. This analysis establishes RNA methylation, particularly m6A, as a pivotal and reversible regulatory mechanism in plant drought stress responses and identifies key future research avenues for both fundamental understanding and crop improvement.
    Keywords:  N6-methyladenosine; RNA methylation; crop improvement; drought stress; epitranscriptomics
    DOI:  https://doi.org/10.3389/fpls.2026.1766123
  3. J Biol Chem. 2026 Mar 03. pii: S0021-9258(26)00207-3. [Epub ahead of print] 111337
    Mapping the temporality and structural impacts of modifications in E. coli tRNAs.
    Marcel-Joseph Yared, Carine Chagneau, Pierre Barraud.
      Transfer RNAs (tRNAs) are essential components of the protein synthesis machinery. Their biogenesis is a highly regulated process that involves the incorporation of numerous post-transcriptional chemical modifications, essential for tRNA folding, cellular stability and function. The sequential process by which these modifications are introduced remains poorly characterized. Previous studies have suggested the existence of modification hierarchies, particularly in the anticodon-loop region, but also among tRNA core modifications. Here, aiming to understand the molecular mechanisms by which modifications are incorporated in a bacterial model organism, we employed a combination of NMR spectroscopy and biochemical methods to characterize the maturation process of several E. coli tRNAs. By monitoring tRNA maturation in a time-resolved fashion by NMR, we observed a conserved temporal pattern in the incorporation of the Ψ55, T54, and m7G46 modifications. We also show that Ψ55 stimulates the incorporation of T54 in E. coli tRNAPhe, tRNAVal and tRNAAsp, and stimulates that of m7G46 in tRNAPhe and tRNAAsp. Importantly, we also provide general insights into the impact of modifications on tRNA structural properties, and show that while post-transcriptional modifications generally have a structuring effect that reduces conformational heterogeneities, these effects are tRNA-dependent, with certain tRNAs being more affected than others. These findings provide fundamental insights into the molecular aspects of tRNA maturation in E. coli.
    Keywords:  Escherichia coli; NMR; RNA modifications; TrmA; TrmB; TruB; kinetic assays; m(5)U; modification circuit; pseudouridine; tRNA structure; transfer RNA
    DOI:  https://doi.org/10.1016/j.jbc.2026.111337
  4. Proc Natl Acad Sci U S A. 2026 Mar 10. 123(10): e2524659123
    MondoA mediates transcriptional coordination between the MYC network and the integrated stress response in pancreatic cancer.
    Erin L Ramsey, Stephanie Dobersch, Brian Freie, Nan Hyung Hong, Xiaoying Wu, Sita Kugel, Robert N Eisenman, Patrick A Carroll.
      MYC amplification contributes to poor survival and outcome in pancreatic ductal adenocarcinoma (PDAC). Here we show that in PDAC cell lines with amplified MYC, MondoA is required for viability, facilitating proliferation while suppressing apoptosis in vitro and in vivo. Transcriptional and genomic profiling demonstrates that loss of MondoA leads to altered expression of direct MondoA targets as well as MYC target genes and is accompanied by shifts in genomic occupancy of MYC, MNT, and the MondoA paralog ChREBP. This altered genomic binding by MYC network members is associated with transcriptional perturbation of multiple metabolic and stress pathways, as well as global changes in N6-methyladenosine modification (m6A) of messenger RNA (mRNA). MondoA inhibition disrupts coordination between MYC network members and the Integrated Stress Response (ISR), resulting in decreased translation of ATF4 mRNA, discordant gene regulation of shared targets of MYC and ATF4 and, ultimately, apoptosis. Reestablishing ATF4 protein expression rescues the diminished viability due to loss of MondoA expression or activity, providing direct evidence of a link between deregulated MYC and the transcriptional machinery of the ISR. Last, we find that small-molecule inhibition of MondoA is lethal in a subset of PDAC cell lines, including patient-derived organoids, suggesting that the ability to target MYC via chemical inhibition of MondoA transcriptional activity may have broad efficacy.
    Keywords:  MYC network; MondoA inhibitor; MondoA/MLXIP; pancreatic cancer; stress response
    DOI:  https://doi.org/10.1073/pnas.2524659123
  5. Parasit Vectors. 2026 Mar 04.
    The related EIF4G3 and EIF4G4 initiation factors from Leishmania: dissimilar modes of action during translation revealed by a comparative proteomic approach.
    Stéphanny Sallomé Sousa Oliveira, Larissa Melo do Nascimento, Danielle Maria Nascimento Moura, Christian Robson de Souza Reis, Osvaldo Pompílio de Melo Neto.
       BACKGROUND: The start of eukaryotic translation requires recruitment of messenger RNA (mRNA) through the action of the eukaryotic initiation factor 4F (eIF4F) complex. eIF4F is formed by joining of the eIF4G and eIF4E subunits and generally also requires the eIF4A helicase. In Leishmania infantum, five eIF4Gs form multiple eIF4F-like complexes, with those based on the related EIF4G3 and EIF4G4 being active during translation, but with likely nonredundant roles that need to be better defined.
    METHODS: To further investigate the roles of EIF4G3 and EIF4G4 in Leishmania infantum, we generated transgenic cell lines expressing each protein tagged with a C-terminal hemagglutinin (HA) epitope. Expression analyses were then carried out during different phases of promastigote growth, followed by gene knockout and complementation assays investigating the essentiality of the targeted eIF4Gs. The HA-tagged proteins were then used as baits in a large-scale investigation of potential protein partners, from different growth phases: early exponential, late exponential, and stationary.
    RESULTS: EIF4G3 and EIF4G4 were expressed as multiple isoforms during promastigote growth, with EIF4G4 isoforms changing according to the growth phase. The two HA-tagged proteins were capable of replacing the corresponding native proteins after deletion of the endogenous genes. EIF4G3-HA and EIF4G4-HA were always found with their known eIF4E partners, respectively EIF4E4 and EIF4E3. EIF4G3-HA also more consistently coprecipitated with poly(A)-binding protein 1 (PABP1), RNA-binding protein 23 (RBP23), and EIF4AI, with EIF4G4-HA having greater association with PABP3 and the HEL67 helicase. A variable number of translation factors and ribosomal proteins were found with both baits, reflecting roles in translation. Our extensive analyses, investigating also proteins with possible moonlighting roles and uncharacterized polypeptides, not only revealed new proteins bound to both baits but also identified new specific partners for EIF4G3, and possibly EIF4G4, some of those being restricted to selected growth phases.
    CONCLUSIONS: Overall, new and more defined binding partners were observed for EIF4G3, with EIF4G4 having an increased coprecipitation with other translation initiation factors. Newly identified partners, for both eIF4Gs, might facilitate specific mRNA recognition or function regulating translation during growth. Further studies on some of those might reveal unique and conserved aspects of the Leishmania translation and might help define targets for novel translation inhibitors.
    Keywords:  Mass spectrometry; Protein synthesis; RNA binding protein; eIF4F complex; eIF4G; mRNA translation
    DOI:  https://doi.org/10.1186/s13071-026-07297-1
  6. Annu Rev Chem Biomol Eng. 2026 Mar 06.
    Strategies to Improve the Stability and Translation of Therapeutic mRNAs.
    Baizhen Gao, Shujun He, Qing Sun.
      Therapeutic messenger RNAs (mRNAs) offer a versatile platform for treating a wide range of diseases, but their clinical efficacy hinges on optimizing both stability and translational efficiency. This review summarizes recent advances in strategies to enhance mRNA performance, with a focus on human therapeutics. We discuss secondary structure optimization, including artificial intelligence-guided design tools like RNAdegformer and LinearDesign, which balance structural stability and translational output. The roles of 5' and 3' untranslated regions in ribosome recruitment and mRNA decay are examined, highlighting sequence motifs and empirical design strategies that facilitate these processes. Chemical modifications, such as pseudouridine substitution, are shown to improve stability and reduce immunogenicity. Emerging approaches using circular RNA further extend transcript longevity. Finally, we review delivery technologies, including lipid nanoparticles, polymers, and extracellular vesicles, that protect mRNA and enable targeted cellular uptake. Together, these advances provide a road map for developing stable, efficient, and clinically viable mRNA-based therapeutics.
    DOI:  https://doi.org/10.1146/annurev-chembioeng-100724-084241
  7. J Exp Bot. 2026 Mar 04. pii: erag102. [Epub ahead of print]
    PELOTA at the Crossroads of Ribosome-associated quality control and Silencing: Coordinating Development, Stress, and Immunity in Plants.
    Gemma Sans-Coll, Catharina Merchante.
      Ribosome-associated quality control (RaQC) pathways, including no-go decay (NGD) and non-stop decay (NSD), are essential for maintaining translational fidelity and regulating gene expression in eukaryotes. Central to these pathways is the conserved ribosome rescue factor PELOTA, which resolves stalled ribosomes and promotes the clearance of aberrant mRNAs and nascent polypeptides. While NGD and NSD have been extensively characterized in yeast and animals, our understanding of these processes in plants remains limited. Nevertheless, emerging evidence indicates that PELOTA plays a pivotal role in plant biology, contributing to key developmental processes and regulating immune responses to bacterial and viral pathogens. In this review, we provide an overview of the core NGD and NSD machinery in eukaryotes and synthesize current knowledge of these pathways in plants, highlighting both conserved mechanisms and regulatory features that appear to be plant-specific. We further discuss the roles of PELOTA in plant development and biotic stress responses and draw on insights from other eukaryotic systems to identify major gaps and open questions. By consolidating existing findings and outlining future research directions, this review aims to underscore the importance of ribosome-associated quality control in plants and aims to stimulate further investigation into this still underexplored field.
    Keywords:  No-go decay; Non-stop decay; PELOTA; Plant development; Plant immunity; RNA silencing; Ribosome-associated quality control
    DOI:  https://doi.org/10.1093/jxb/erag102
  8. NAR Genom Bioinform. 2026 Mar;8(1): lqag024
    Mapping the inter- and intra-genic codon-usage landscape in Homo sapiens.
    Maahil Arshad, Matthew Uchmanowicz, Vanshika Rana, Brett Trost, Stephen W Scherer, Muhammad Arshad Rafiq.
      Although the genetic code is degenerate, codon selection is nonrandom and reflects significant functional constraints. Codon-usage bias (CUB) acts as a layer of post-transcriptional regulation, influencing messenger RNA (mRNA) stability, translation kinetics, and co-translational protein folding. While CUB is well-characterized in unicellular organisms, its regulatory scope and functional consequences in humans remain complex and less defined. Our study offers a comprehensive evaluation of human codon usage. We report that genes exhibiting the strongest codon bias are enriched in high-stoichiometry biological processes, such as skin development and oxygen/carbon dioxide transport, and harbor significantly fewer synonymous variants than expected (ρ = -0.24, P < 2.2 × 10-16). Furthermore, we find that codon optimization is structurally distinct: it is significantly more pronounced in structured protein domains compared to intrinsically disordered regions (IDRs) (Cliff's Δ= 0.26, P < 2.2 × 10-16). Consistent with translational selection, the most frequently used codons are supported by higher transfer RNA (tRNA) gene copy numbers (ρ = 0.49, P < 6.4 × 10-4). Finally, by correcting for GC3 content, we reveal that the apparent correlation between effective number of codon and adaptation indices (CAI/tAI) vanishes, allowing us to disentangle mutational pressure from translational selection. Collectively, our findings position CUB as a central, evolutionarily conserved regulator of translation and protein folding in humans. Our results provide a comprehensive and integrated view of intergenic and intragenic CUB in humans, reinforcing the biological relevance of synonymous codon choice in shaping translational dynamics and protein biogenesis. This provides a refined framework for interpreting synonymous variation and guiding functional genomics.
    DOI:  https://doi.org/10.1093/nargab/lqag024
  9. Adv Biotechnol (Singap). 2026 Mar 06. pii: 7. [Epub ahead of print]4(1):
    The expanding role of m6A RNA modification in plant-virus dynamics: friend, foe, or both?
    Jia-Hui Liu, Hao Yu, Cheng-Guo Duan.
      N6-methyladenosine (m6A), the most prevalent internal mRNA modification, regulates plant development and stress responses through modulating various mRNA metabolic processes and epigenetic effects. Although well studied in animals, its roles in plant-virus interactions have only recently begun to be elucidated. Multiple plant viruses carry m6A modifications on their RNAs, validated by MeRIP-seq, LC-MS/MS, and direct RNA sequencing. Viral RNAs acquire m6A through the recruitment or relocalization of host methyltransferase complexes, which is often mediated by viral proteins. Functionally, m6A can restrict infection by promoting viral RNA decay via YTH-domain readers and RNA surveillance pathways, or alternatively stabilize viral RNAs to enhance replication and systemic spread. In turn, viruses disrupt the functionality of host m6A machinery to promote infection. Moreover, viral infection reprograms host m6A homeostasis, altering methylation landscapes in immune and hormone pathways. These findings establish m6A as a dynamic epitranscriptomic switch in plant-virus interactions, with promising implications for antiviral strategies and crop improvement.
    Keywords:  Epigenetics; Epitranscriptome; Plant virus; Plant-virus interaction; RNA modification; m6A
    DOI:  https://doi.org/10.1007/s44307-026-00100-3
  10. Front Mol Biosci. 2026 ;13 1749992
    Nucleolus as a cornerstone linking proliferation and metabolism to cellular responses to stress: involvement of transcription factors MYC and p53.
    Аnastasiia Moraleva, Nadezhda Antipova, Pankrat Pavlov, Kira Dobrochaeva, Yury Rubtsov.
      The nucleoli are a dynamic membraneless organelles in the nucleus playing a key role in cellular homeostasis. Transcription of rDNA, processing of rRNA, and assembly of the ribosomal subunits occur in nucleoli. Aside from ribosome biogenesis, the nucleolus is also involved in the regulation of other crucial functions, including DNA repair, regulation of cell cycle and apoptosis by mediating nucleolar stress responses. This makes it a key hub participating in regulation of various cellular processes. Given the fact, that protein biosynthesis is directly linked to multiple pathways and depends on ribosome production, it is not surprising that ribosome biogenesis is a centerpiece connecting fundamental cellular processes with each other. Of particular interest is the relationship between the nucleolus, cell cycle, and oncogenesis. In tumor and hyperproliferative cells, an increase in nucleolar size and activity directly correlates with enhanced ribosome biogenesis. This process is mutually controlled by oncogenes of the MYC family and tumor suppressors such as p53 and ARF. MYC plays a central role in regulating DNA transcription, and disrupting of ribosome biogenesis regulation could result in nucleolar stress. It induces activation of p53-dependent and p53-independent checkpoint pathways resulting in cell cycle arrest or apoptosis. In addition to its role in carcinogenesis, impaired ribosome biogenesis is associated with neurodegenerative diseases and ribosomopathies such as Diamond-Blackfan anemia. Thus, understanding the molecular mechanisms of nucleolar functions, and its links with main regulators of the cell cycle and oncogenesis is of great importance. It may help finding novel molecular targets and therapeutic approaches to treat disorders associated with dysregulated ribosome biogenesis and control of proliferation. This review considers the main aspects of nucleolar activity regulation, its role in the cell cycle and diseases, and the therapeutic prospects for targeting these processes.
    Keywords:  ARF; MYC; mTOR; nucleolar stress; nucleolus; p53; ribosome biogenesis
    DOI:  https://doi.org/10.3389/fmolb.2026.1749992
  11. Nat Cell Biol. 2026 Mar 02.
    RNA-specific local translation is patterned by condensates for multinucleate cell growth.
    Zachary M Geisterfer, Ameya P Jalihal, Sierra J Cole, Amy S Gladfelter.
      Coordination between growth and nuclear division is a common cell feature. In some syncytia, nuclei divide asynchronously throughout the cell but growth occurs only at discrete locations, raising the question how the processes are locally regulated and globally coordinated. In the syncytial fungus Ashbya gossypii, both cell cycle progression and hyphal elongation require condensates formed by the protein Whi3 in complex with distinct mRNA species. Here we show that Whi3 condensates are enriched for translation regulators and are associated with local, spatially patterned translation of specific target RNAs near nuclei and growth sites. Whi3-RNA condensates can both promote and repress mRNA translation in an RNA- and condensate size-dependent manner in vitro. Condensate interfaces are sites of translation, tunable by condensate composition, RNA valency and protein charge state in vitro. Together, these data suggest that Whi3 condensates can generate a continuum of translation states that vary depending on the subcellular location and resident RNA sequences.
    DOI:  https://doi.org/10.1038/s41556-026-01887-y
  12. Proc Natl Acad Sci U S A. 2026 Mar 10. 123(10): e2518495123
    Coevolution of RNase P and the ribosome.
    Anton S Petrov, Claudia Alvarez-Carreño, Loren Dean Williams, Mark A Ditzler.
      Translation is carried out by the most conserved assemblies in biology. Among these assemblies, the ribosome and RNase P are central players. These ancient ribonucleoprotein complexes achieved structural and functional maturity by the last universal common ancestor (LUCA) of life. In prior work, we reconstructed the evolutionary history of the ribosome using its three-dimensional structure, based on accretion and molecular fingerprints that date back to life's earliest stages. Here, we extend our structural phylogenetic framework-based on the accretion model-to RNase P, a ribonucleoprotein responsible for processing pre-tRNAs. By sampling RNase P RNA (RPR) sequences and structures across phylogeny and partitioning them into RNA fragments based on insertion fingerprints, we characterize the state of RPR at LUCA and reconstruct the chronology of its emergence. The chronology reveals that RNase P, like the ribosome, accreted modular RNA elements over evolution, while preserving the structure of preexisting elements, thus maintaining a structural record. We used interactions with tRNA to link and unify the evolutionary trajectories of RPR and rRNA. These results support the view that RNase P and the ribosome coevolved as part of a functionally integrated system. The ancestral catalytic sites of rRNA and RPR formed by the same process, fusion of two stem-elbow-stem elements. Analysis of these two coevolving RNAs also suggests that some of their accreted elements share common ancestry. Application of the accretion model requires correct secondary structures and was successful for RPR only when the traditional secondary structure was corrected by reorganizing a pseudoknot.
    Keywords:  RNA evolution; origin of life; tranlsation
    DOI:  https://doi.org/10.1073/pnas.2518495123
  13. DNA Cell Biol. 2026 Mar;45(3): 105-115
    N6-Methylation Modification: Its Role in Regulating Cell Senescence and Inflammation in Osteoarthritis and Intervertebral Disc Degeneration.
    Rui Sun, Yan Zhou, Xiao-Tao Wu, Hang Shi, Feng Wang, Jia-Wei Gao, Pei-Yang Wang, Zheng-Yuan Xu, Cong Zhang.
      N6-methyladenosine (m6A) methylation, the most prevalent internal mRNA modification in eukaryotes, plays a crucial role in regulating various biological processes. Recent advancements reveal its significant involvement in osteoarthritis (OA) and intervertebral disc degeneration (IVDD). m6A modifications influence key cellular processes such as inflammation, stress responses, and matrix homeostasis, which are pivotal in OA and IVDD pathogenesis. In OA, m6A methylation affects inflammatory responses, macrophage polarization, and chondrocyte ferroptosis, while in IVDD, it regulates RNA methylation and matrix integrity. Additionally, m6A interacts with noncoding RNAs, impacting their stability and function, thus influencing disease outcomes. Emerging evidence suggests that targeting m6A pathways could provide novel therapeutic strategies for managing OA and IVDD. Further research into m6A's role in these diseases may reveal new biomarkers and therapeutic targets, offering potential for more effective treatments and improved patient outcomes.
    Keywords:  inflammation; intervertebral disc degeneration; m6A methylation; osteoarthritis; senescence
    DOI:  https://doi.org/10.1177/10445498251411282
  14. Plant Commun. 2026 Mar 03. pii: S2590-3462(26)00095-7. [Epub ahead of print] 101787
    Plant P-Bodies in Post-Transcriptional Control: Composition, Dynamics, and Context-Dependent Roles.
    Arash Matinahmadi, Zoofa Zayani, Karolina Majewska, Dariusz Jan Smoliński.
      Processing bodies (P-bodies, PBs) are cytoplasmic RNP condensates that concentrate mRNA-decay and translation-repression factors. In plants, PBs share core machinery with other eukaryotes yet exhibit unique, context-dependent features that distinguish them from their yeast and mammalian counterparts. These are shaped by direct modulation from hormonal signaling (e.g., ABA) and stress physiology, highlighting their specialized roles in adaptation. Here we synthesize plant-focused evidence on PB composition, liquid-liquid phase separation (LLPS-driven assembly), and coupling to decapping-dependent and co-translational decay. We clarify when PBs act as decay hotspots versus buffering sites for non-translating mRNAs, and we explicitly separate plant findings from yeast/animal inferences. We also integrate recent data on post-translational modifications (e.g., MAPK-dependent DCP1 phosphorylation) and RNA modifications (m6A/ECT8) in selective mRNA targeting. Finally, we outline open questions on the spatial organization of decay, PB-stress granule crosstalk, and hormonal control, and highlight methodological avenues. Overall, plant PBs emerge as dynamic hubs that help tune post-transcriptional control to developmental and environmental cues, with mechanisms increasingly resolved by interdisciplinary combinations of live-cell imaging, quantitative proteomics, and CRISPR-based genetics.
    Keywords:  Arabidopsis thaliana; P-bodies; Stress responses; biomolecular condensates; mRNA decay; translation repression
    DOI:  https://doi.org/10.1016/j.xplc.2026.101787
  15. NPJ Biol Timing Sleep. 2025 May 27. pii: 20. [Epub ahead of print]2(1):
    Regulatory links between the circadian clock and stress-induced biomolecular condensates.
    Gabriela Brown, Dawn H Nagel.
      The circadian clock is a conserved timekeeping mechanism that is essential for integrating different environmental cues such as light and temperature to coordinate biological processes with the time of day. While much is known about transcriptional regulation by the clock, the role of post-transcriptional regulation, particularly through sequestration into biomolecular condensate such as stress granules, remains less understood. Stress granules are dynamic RNA-protein assemblies that play a critical role in the cellular response to stress by sequestering mRNAs to regulate translation during stressful conditions. In animals and fungi, the circadian clock regulates stress granule formation and mRNA translation by controlling key factors such as eIF2α, which orchestrates the rhythmic sequestration and translation of specific mRNAs. In plants, it has been shown that some transcripts, despite coming from arrhythmic expression, are rhythmically translated. In addition, some clock-controlled genes (CCGs) are induced in response to heat stress only at the transcriptional level and not at the translational level. Together this highlights a layer of clock regulation beyond transcription. This review discusses the intersection between the circadian clock and heat stress-related biomolecular condensates across eukaryotes, with a particular focus on plants. We discuss how the clock may regulate stress granule dynamics and preferential translation of mRNAs at specific times of the day or during stress responses, thereby enhancing cellular function and energy efficiency. By integrating evidence from animals, fungi, and plants, we highlight emerging questions regarding the role of biomolecular condensates as post-transcriptional mechanisms in controlling circadian rhythms and stress tolerance in plants.
    DOI:  https://doi.org/10.1038/s44323-025-00036-2
  16. Proc Natl Acad Sci U S A. 2026 Mar 10. 123(10): e2529187123
    METTL3-mediated N6-methyladenosine modification of Dnajb1 modulates cardiomyocyte ferroptosis during myocardial infarction.
    Shuchen Zhang, Boyang Xiang, Yiheng Zhao, Lili Chen, Danni Meng, Xiang Zhou.
      Myocardial infarction (MI) affects millions of individuals worldwide, with ferroptosis recognized as a pivotal regulated cell death pathway in this context. N6-methyladenosine (m6A), the most prevalent mRNA modification, is essential in modulating RNA splicing, export, stability, and translation during MI progression. Nonetheless, the involvement of m6A modification in cardiomyocyte ferroptosis has yet to be elucidated. This study aimed to elucidate the regulatory mechanisms of m6A modification in cardiomyocyte ferroptosis by conducting an integrated analysis of methylated RNA immunoprecipitation-sequencing and RNA-sequencing data obtained from myocardial tissues of MI mice, to identify promising therapeutic strategies for MI. We demonstrated that the differentially m6A-modified DnaJ heat shock protein family member B1 (Dnajb1) gene suppressed ferroptosis during the pathological process of MI. DNAJB1 overexpression protected against hypoxia-induced cardiomyocyte ferroptosis by suppressing pro-ferroptotic effectors. Mechanistically, methyltransferase-like 3 (METTL3) bound to Dnajb1, enhancing its m6A modification and diminishing mRNA stability, while insulin-like growth factor 2 mRNA-binding protein 3 competes for binding and increases mRNA stability. DNAJB1 prevented hypoxia-induced glutathione depletion and lipid peroxidation by inhibiting glutathione peroxidase 4 degradation via the autophagic-lysosomal pathway. In vivo, DNAJB1 overexpression improved heart function, reduced infarct size and fibrosis, and lowered plasma malondialdehyde levels in MI mice, whereas METTL3 co-overexpression counteracted these cardioprotective effects. Overall, this study uncovers a METTL3/Dnajb1 pathway in cardiomyocyte ferroptosis during MI. METTL3 modifies Dnajb1 through m6A, destabilizing its mRNA and weakening glutathione peroxidase 4-dependent antioxidant defense, thus promoting ferroptosis. These insights into epitranscriptomic regulation of cell death highlight potential therapeutic targets to prevent ferroptosis-related cardiac damage.
    Keywords:  DNAJB1; METTL3; ferroptosis; m6A; myocardial infarction
    DOI:  https://doi.org/10.1073/pnas.2529187123
  17. Inflammation. 2026 Mar 04.
    METTL3-Mediated m6A Regulation of CircINTS4/miR-146b-3p Axis in Rheumatoid Arthritis.
    Shu Li, MengYu Zhang, SiYu Liang, Lei Wan, XiaoJun Zhang.
       BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial inflammation and joint destruction. Despite advances in understanding its pathogenesis, the role of epigenetic regulation and non-coding RNA networks remains inadequately explored. This study investigates the involvement of N6-methyladenosine (m6A) modification and circular RNA (circRNA), specifically circINTS4, in RA.
    METHODS: We conducted a bibliometric analysis to map research trends in m6A and miR-146 family studies in RA. Whole-transcriptome sequencing was performed on synovial tissue from RA patients and healthy controls (HCs) to identify differentially expressed circRNAs. miRNA expression was profiled using publicly available datasets. The role of METTL3 in regulating circINTS4 was examined through loss-of-function experiments in RA fibroblast-like synoviocytes (RA-FLS). A dual-luciferase reporter assay validated the direct interaction between circINTS4 and miR-146b-3p. Functional assays in RA-FLS and in vivo models assessed the impact of circINTS4 depletion on disease progression.
    RESULTS: circINTS4 was the most significantly downregulated circRNA in RA, and miR-146b-3p was the most upregulated miRNA in RA patients. METTL3 depletion in RA-FLS reduced global m6A methylation and decreased m6A enrichment on circINTS4, leading to increased circINTS4 expression and decreased miR-146b-3p levels. Clinical analysis revealed an inverse relationship between circINTS4 and miR-146b-3p expression. Functionally, circINTS4 served as a sponge for miR-146b-3p, with its depletion enhancing RA-FLS proliferation, migration, and resistance to apoptosis. In vivo, circINTS4 knockdown exacerbated synovial inflammation and elevated pro-inflammatory cytokine levels in a rat model of RA.
    CONCLUSION: Our findings reveal that METTL3-mediated m6A modification regulates the circINTS4/miR-146b-3p axis, modulating RA-FLS pathogenicity and inflammatory responses. CircINTS4 acts as a molecular sponge for miR-146b-3p and serves as a promising biomarker for RA disease severity. This study provides new insights into the role of m6A methylation and circRNA-miRNA networks in RA, highlighting their potential as diagnostic and therapeutic targets.
    Keywords:  Circular RNA (circRNA); METTL3; MiR-146b-3p; N6-methyladenosine (m6A) modification; Rheumatoid arthritis (RA)
    DOI:  https://doi.org/10.1007/s10753-026-02484-9
  18. Kaohsiung J Med Sci. 2026 Mar 02. e70196
    Oncogenic KRAS Rewires Stress Granule Dynamics: Mechanisms and Therapeutic Opportunities.
    Msimisi Ndzinisa, Birhanetensay Masresha Altaye, Yuh-Pyng Sher.
      Stress granules (SGs) are dynamic, membrane-less structures that form in response to various cellular stresses, including metabolic, oxidative, and therapeutic challenges. They function as adaptive hubs and reorganize protein synthesis and signaling networks to help cells survive under stress. In cancer, these condensates are often hijacked to support survival and therapy resistance. SGs can sequester proapoptotic factors, buffer metabolic- and treatment-induced stress, and stabilize transcripts that promote cell survival, collectively contributing to tumor aggressiveness and resistance to therapy. Their formation relies on protein-RNA interactions, phase separation, and posttranslational modifications, which tumor cells exploit to maintain SGs even when normal stress conditions trigger their disassembly. This creates a protective pool of mRNAs and proteins that allows rapid adaptation to stress. Emerging therapeutic strategies that disrupt SG assembly, interfere with the adaptive functions of SGs, or accelerate SG clearance have shown promise in sensitizing tumors to treatment. This review summarizes the current understanding of SG dynamics, illustrating how cancer cells exploit these structures to survive stress. We focus specifically on KRAS-driven cancers, where persistent oncogenic signaling enhances SG formation and stability, making these condensates critical mediators of tumor adaptation. Targeting SG formation, maintenance, or associated stress-response pathways represents a promising approach to enhance therapeutic efficacy and improve long-term outcomes in cancers driven by sustained cellular stress.
    Keywords:  KRAS mutation; RNA‐binding proteins; cancer therapy resistance; stress granules; targeted therapies
    DOI:  https://doi.org/10.1002/kjm2.70196
  19. Biocell. 2026 ;pii: 2. [Epub ahead of print]50(1):
    The Yin-Yang of Stress and Senescence: Integrated Stress Response and SASP Crosstalk in Stem Cell Fate, Regeneration, and Disease.
    Douglas M Ruden.
      Stem cell fate decisions are increasingly understood through the dynamic interplay of two fundamental stress-adaptive programs: the integrated stress response (ISR) and the senescence-associated secretory phenotype (SASP). These pathways act as a Yin-Yang system, balancing beneficial and detrimental outcomes across development, tissue homeostasis, and disease. On the yin (protective) side, transient ISR activation and acute SASP signaling foster adaptation, embryonic patterning, wound healing, and regeneration. On the yang (maladaptive) side, chronic ISR signaling and unresolved SASP output drive stem cell exhaustion, fibrosis, inflammation, and tumorigenesis. This duality highlights their roles as both guardians and disruptors of stem cell integrity. Mechanistically, ISR regulates translational control via eukaryotic initiation factor 2 alpha (eIF2α) phosphorylation and activating transcription factor 4 (ATF4)-dependent transcription, while SASP reprograms the extracellular milieu through cytokines, growth factors, and proteases. Their crosstalk creates feedback loops that shape tissue niches and long-term stem cell potential. Framing ISR-SASP interactions through a Yin-Yang lens underscores the balance between resilience and decline, to offer new insights into regenerative medicine, anti-aging interventions, and cancer therapeutics.
    Keywords:  Integrated stress response (ISR); activating transcription factor 4 (ATF4); cancer; eukaryotic initiation factor 2 alpha (eIF2α); inflammation; senescence-associated secretory phenotype (SASP); stem cells
    DOI:  https://doi.org/10.32604/biocell.2025.072273
  20. Epigenetics. 2026 Dec;21(1): 2629068
    Emerging roles of RNA N5-methylcytosine modification in reproductive physiology and gynecological diseases.
    Fei Lv, Yi Jin, Shuchen Yu, Xinyi Yang, Shiyu Xia, Xiaoye Ye, Qihang Zhao, Ying Hu, Aolin Zheng, Yongfeng Wu, Jinyi Tong.
      The epitranscriptome, comprising post-transcriptional RNA modifications, has emerged as a pivotal regulator of gene expression in the female reproductive system. Among these modifications, 5-methylcytosine (m5C) stands out as a widespread and highly conserved mark whose roles in female reproductive health and disease are increasingly recognized but have not yet been systematically summarized. This review aims to synthesize current knowledge on the functions and regulatory mechanisms of m5C in female reproductive physiology and associated pathologies. We begin with a foundational overview of m5C, detailing its definition, biological functions, and the dynamic regulatory network of 'writers,' 'readers,' and 'erasers.' We then examine the critical roles of m5C in key physiological processes, including oogenesis and early embryonic development. Furthermore, we provide an in-depth analysis of the mechanistic involvement and clinical implications of m5C dysregulation in various gynecological diseases. By consolidating recent advances, this review seeks to establish a comprehensive framework for understanding m5C in the female reproductive system and to offer a valuable reference and theoretical basis for future research and therapeutic exploration.
    Keywords:  5-methylcytosine (m5C); NSUN2; YBX1; female reproduction; gynecological disease
    DOI:  https://doi.org/10.1080/15592294.2026.2629068
  21. PLoS Pathog. 2026 Mar 06. 22(3): e1013551
    The UTRs of Leishmania donovani vary in length and are enriched in potential regulatory structures.
    Franck Dumetz, Kaylee J Watson, Melissa Perry, Robin E Bromley, Anushka R Shome, Julie C Dunning Hotopp, Iqbal Hamza, David Serre.
      Leishmania spp. regulate gene expression post-transcriptionally, yet untranslated regions (UTRs) that can affect mRNA stability and translation remain poorly delineated. We generated a de novo assembled genome for Leishmania donovani strain 1S2D (Ld1S) using PacBio HiFi and characterized the transcriptomes of promastigotes and axenic amastigotes with Oxford Nanopore direct RNA sequencing. The genome assembly consists of 65 scaffolds totaling ~33.3 Mb. Structural comparisons to LdBPK282A1 revealed numerous rearrangements, including genes reshuffled among polycistronic transcription units and validated by RNA sequencing of polycistronic reads. Promastigote and amastigote RNA sequencing produced 469,010 and 46,729 monocistronic reads containing a spliced-leader and a polyA tail sequences, defining 8,479 transcripts and supporting 7,415 of the 7,969 annotated protein-coding genes, as well as 604 putative long non-coding RNAs. We annotated UTRs for 4,921 genes and observed that putative RNA G-quadruplexes were markedly enriched in these regions. We also noted that 31.9% and 11.5% of genes were expressed into multiple isoforms in promastigotes and amastigotes, respectively. Collectively, these data provide a genome-wide annotation of L. donovani genes and their UTRs and reveal widespread and stage-specific UTR length polymorphisms and, overall, points to an important role of 3' UTRs in post-transcriptional regulation in L. donovani.
    DOI:  https://doi.org/10.1371/journal.ppat.1013551
  22. Angew Chem Int Ed Engl. 2026 Mar 01. e24223
    Small-Molecule Activation of mRNA Translation by Click-to-Release Reaction in Cells.
    Tess Vosman, Friedrich Burba, Martin Sumser, Milan Vrabel, Hannes Mikula, Andrea Rentmeister.
      mRNA is an emerging medical modality, however, approaches to control its activity lack behind other biologics. Bioorthogonal click-to-release reactions enable breaking chemical bonds at high reaction rates even in living cells to release a functionally active biomolecule ("uncaging"). We developed a 5' cap modified with a trans-cyclooctene (TCO-cap) that reacts with hydroxyaryl-tetrazines to efficiently release the native cap 0. This strategy is compatible with in vitro transcription and facilitates HPLC-based purification of the resulting TCO-capped mRNA, circumventing the need to digest uncapped mRNA produced in the process. Using eGFP- and luciferase-mRNAs in mammalian cells, we show that TCO-capped mRNAs are translationally muted and can be activated for translation by addition of cell-permeable, non-toxic sulfonamide-modified hydroxyphenyl-tetrazines. This work presents a new approach for small-molecule-induced translation in eukaryotes with potential to be applicable to any mRNA.
    Keywords:  5′ cap; click chemistry; mRNA; tetrazines; translation
    DOI:  https://doi.org/10.1002/anie.202524223
  23. Plant Physiol. 2026 Mar 04. pii: kiag082. [Epub ahead of print]
    Light-induced m6A RNA modification regulates anthocyanin accumulation during rose petal coloration.
    Yuerong Gao, Fengqing Wang, Ping Xia, Jie Zhang, Zhen Peng, Ziyan Liu, Chunxin Yu, Ye Wang, Runzhi Li, Shiwei Zhao, Liusheng Duan.
      Light plays a crucial role in regulating anthocyanin biosynthesis during flower coloration. However, the involvement of epigenetic modifications in light-induced flower coloration remains poorly understood. Here, we studied the rose cultivar Rosa hybrida cv. Spectra, which exhibits dramatic light-induced changes in petal coloration. Integrated analysis of the m6A methylome and the transcriptome revealed significant changes in both m6A modifications and the expression of the anthocyanidin synthase gene RhANS (C_AA159414.1) in response to direct light in the petals. Light induced m6A modifications in the coding sequence (CDS) region of RhANS and repressed m6A modification at the 3' untranslated region (3'UTR). m6A modification in the CDS region enhanced mRNA stability and the translation efficiency of RhANS, whereas modification in the 3'UTR exerted an opposing effect. The expression of the m6A demethylase genes RhALKBH10A (C_AA159415.1) and RhALKBH10B (C_AA159416.1) was repressed in petals under direct light conditions. Silencing RhALKBH10A/10B enhanced anthocyanin accumulation, increased m6A abundance at CDS sites, and concurrently reduced m6A abundance at the 3'UTR site of RhANS mRNA. Silencing RhANS abrogated the anthocyanin accumulation induced by RhALKBH10A/10B silencing. Our results reveal that light modulates m6A modifications to regulate mRNA stability and translation of RhANS, thereby driving petal coloration in rose.
    Keywords:   ALKBH10A/10B ; ANS ; Rosa hybrida ; m6A RNA modification; petal color
    DOI:  https://doi.org/10.1093/plphys/kiag082
  24. Nucleic Acids Res. 2026 Feb 24. pii: gkag194. [Epub ahead of print]54(5):
    FUS is an N1- and N6-methyladenosine-binding protein.
    Xiaochen Liang, Ting Zhao, Xiaoxia Dai, Yuxiang Sun, Jun Yuan, Sanat Afzalpurkar, Connor Duong, Albert Yu, Feng Tang, Xiaomei He, Xiaochuan Liu, Xingyuan Chen, Zhongwen Cao, Yinsheng Wang.
      Nucleotide repeat expansions contribute to a number of neurological disorders. Mutations and augmented expression in fused in sarcoma (FUS) can result in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Here we reveal that FUS is an N1- and N6-methyladenosine (m1A- and m6A)-binding protein, where the protein interacts with the methylated adenosines in CAG repeat expansion RNA, thereby leading to the protein's cytoplasmic redistribution in SH-SY5Y cells. We also found that ectopically expressed FUS co-localizes with CAG repeat RNA in the cytosol. This co-localization is diminished upon genetic depletion of m6A and m1A writer proteins (i.e. METTL3 and TRMT61A), pharmacological inhibition of METTL3, and ectopic overexpression of m1A and m6A eraser proteins (i.e. ALKBH3 and FTO). Moreover, binding to methylated CAG repeat RNA renders the ectopically expressed FUS protein less dynamic in cells. Together, our study underscores a critical role for m1A and m6A in enhancing FUS-RNA interaction, which results in aberrant subcellular distribution and attenuated mobility of the protein in cells. These findings unveil a novel mechanism underlying neurodegenerative disorders emanating from elevated expression of FUS and suggest targeting FUS-methylated adenosine interactions as a potential therapeutic strategy for FUS proteinopathy.
    DOI:  https://doi.org/10.1093/nar/gkag194
  25. Biotechnol Adv. 2026 Mar 04. pii: S0734-9750(26)00068-6. [Epub ahead of print] 108862
    RNA therapeutics 2.0: Expanding the landscape from mRNA vaccines to splicing modulators and beyond.
    Pawan N Karwa, Nikhil S Sakle.
      RNA therapeutics have progressed into a disruptive drug class quickly, replacing a variety of primary experimental agents which included vaccines, antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), aptamers and RNA editing systems. First-generation modalities, demonstrated by fomivirsen and pegaptanib were limited by vulnerability to nuclease attack, inefficient delivery and immune stimulation were treated with clinical feasibility. Recent clinical achievements, including mRNA vaccinations against COVID-19, have been based on developments in backbone chemistry, nucleoside modifications and targeted delivery including N-acetylgalactosamine (GalNAc) conjugation and lipid nanoparticle (LNP) encapsulation. On this basis, it can be stated that the RNA Therapeutics 2.0 is more stable, tunable and can be targeted to organs and tissues. New methodologies such as circular RNA (circRNAs), self-amplifying mRNAs (saRNAs), splice-switching adenosine specific oligonucleotides (ASOs), small-molecule splicing modulators and adenosine deaminase toward RNA (ADAR)-directed base editors. These new generation systems can be used to make durable protein expression, reversible transcript recoding and precision splicing modulation, extending therapeutic applications to oncology, neurology, metabolic disease and rare genetic disorders. Extrahepatic delivery via innovations in delivery that included ligand-targeted LNPs, peptide conjugates and engineered exosomes is surpassing and artificial intelligence (AI) enhanced design is hastening optimization of RNA sequences, chemistries and vectors. RNA therapeutics in combination with gene therapy can be used to produce personalized therapeutics, such as n-of-1 medicines, based on immune regulation and control circuits. This Review describes the development of early oligonucleotide drugs to a diversified arsenal of RNA platforms, the major advancements, obstacles and emerging technology that characterize the next stage of RNA-based precision medicine.
    Keywords:  Circular RNA; RNA editing; RNA therapeutics; Self-amplifying mRNA; Splicing modulation; Targeted delivery systems
    DOI:  https://doi.org/10.1016/j.biotechadv.2026.108862
  26. Mutat Res. 2026 Feb 23. pii: S1386-1964(26)00003-5. [Epub ahead of print]832 111930
    METTL3 promotes prostate cancer cell metastasis and EMT by mediating NUP210 m6A modification.
    Shaoxing Wang, Jinming Li, Jun Jiang, Jiahao Liu, Shusen Zuo.
       BACKGROUND: Prostate cancer (PCa) is an age-related epithelial malignancy with high metastatic potential. Although nucleoporin 210 (NUP210) is implicated in tumor progression, its role and mechanism in PCa metastasis remain unexplored.
    METHODS: Bioinformatics analysis (Gene Expression Omnibus (GEO)/The University of Alabama at Birmingham CANcer data analysis Portal (UALCAN) databases) and experimental validation (quantitative real-time PCR (qRT-PCR) and western blot) were applied to assess the expression of NUP210, methyltransferase-like 3 (METTL3), metastasis-related markers, and epithelial-mesenchymal transition (EMT)-related markers. Functional assays (transwell, in vivo metastasis models) and mechanistic studies (methylated RNA immunoprecipitation (MeRIP), RNA binding protein immunoprecipitation (RIP), and mRNA stability assays) were performed to elucidate the METTL3/NUP210 axis.
    RESULTS: NUP210 and METTL3 were highly expressed in PCa tissues and cells. Knockdown of NUP210 significantly inhibited PCa metastasis and EMT. Also, the animal study revealed that NUP210 silencing could inhibit the lung metastasis of PCa in vivo. METTL3-mediated N6-methyladenosine (m6A) modification stabilized NUP210 mRNA, and rescue experiments confirmed that NUP210 overexpression reversed the inhibitory effects of METTL3 silencing on PCa cell metastasis and EMT.
    CONCLUSION: The METTL3-mediated m6A modification of NUP210 may promote PCa metastasis and EMT. This newly identified METTL3/NUP210 axis deepens the understanding of PCa progression and suggests its potential for further therapeutic exploration.
    Keywords:  Methyltransferase-like 3; N6-methyladenosine; Nucleoporin 210; Prostate cancer
    DOI:  https://doi.org/10.1016/j.mrfmmm.2026.111930
  27. J Mol Biol. 2026 Feb 26. pii: S0022-2836(26)00107-5. [Epub ahead of print] 169734
    Active Site Assembly by SMG5 as a Mechanism for SMG6 Endonuclease Licencing in Nonsense-mediated mRNA Decay.
    Enes S Arpa, Michael Taschner, Mara De Matos, Stefanie Jonas, David Gatfield.
      Nonsense-mediated mRNA decay (NMD) is a conserved eukaryotic surveillance pathway that eliminates transcripts containing premature termination codons (PTCs). Substantial progress has been made in defining the transcript features that mark aberrant translation termination for NMD activation, yet key mechanistic steps remain incompletely understood - including how recruitment of the central NMD factor UPF1 is coupled to the downstream effector phase in which targeted mRNAs are nucleolytically degraded. In metazoans, NMD employs an endonucleolytic route mediated by SMG6, a PIN-domain nuclease, alongside SMG5 and SMG7, which act downstream of PTC recognition. SMG5 has recently been proposed to licence SMG6 activity, yet the molecular basis of this licencing has remained elusive. Here, we combine AlphaFold structural predictions with biochemical assays to investigate interactions among human SMG5, SMG6, and SMG7. Structural models predict a high-confidence interface between SMG5 and SMG6 PIN domains that forms a composite active site: a conserved SMG5 aspartate (D893) complements the SMG6 acidic triad to reinstate the canonical tetrad required for PIN-domain catalysis. In vitro, SMG6 alone exhibits weak endonucleolytic activity, which is enhanced ∼10-fold by the SMG5 PIN domain. Mutational analyses confirm that conserved residues from both proteins are essential for this composite configuration. Our findings reveal that the SMG5 PIN domain, previously considered catalytically inert, plays a critical role in activating SMG6 by completing its active site. This work provides mechanistic insight into the SMG5-dependent licencing step and uncovers a composite PIN nuclease architecture at the heart of the metazoan NMD effector phase.
    Keywords:  PIN domain; SMG5-SMG6 interaction; UPF1 phosphorylation; endonucleolytic decay; nonsense-mediated mRNA decay (NMD)
    DOI:  https://doi.org/10.1016/j.jmb.2026.169734
  28. ACS Chem Biol. 2026 Mar 06.
    Metabolism of Epigenetic Ribonucleosides Leads to Nucleolar Stress and Cytotoxicity.
    Xuemeng Sun, Anita Donlic, Jacob A Boyer, Theodore E Press, Minjae Kim, Neal K Reddy, Clifford P Brangwynne, Joshua D Rabinowitz, Ralph E Kleiner.
      Post-transcriptional RNA modifications are ubiquitous in biology, but the fate of epigenetic ribonucleotides after RNA turnover and the consequences of their metabolism and misincorporation into nucleic acids are largely unknown. Here, we explore epigenetic ribonucleoside metabolism in human cells by studying effects on cell growth, quantifying RNA misincorporation and identifying metabolic regulators, and exploring phenotypes associated with cytotoxicity. We find that bulky N6-modified adenosines (i.e., i6A) exhibit high levels of cytotoxicity and RNA misincorporation, whereas cells dramatically restrict the misincorporation of small N6-modified adenosines (i.e., m6A), partly through sanitization by enzymatic deamination, consistent with a recent report. Epigenetic ribopyrimidines also exhibit cytotoxicity, dependent on nucleoside kinase UCK2, but only at much higher concentrations than ribopurines. We further characterize the effects of cytotoxic ribonucleoside metabolism on nucleolar morphology and protein translation. Taken together, our work provides new insights into the metabolism of epigenetic ribonucleosides and mechanisms underlying their cytotoxicity to cells.
    DOI:  https://doi.org/10.1021/acschembio.5c00656
  29. Front Immunol. 2026 ;17 1685015
    The emerging role of m6A methylation in prostate-related diseases: mechanisms and clinical implications.
    Qinghua Xie, Hongyan Zhao, Xuan Yang, Hongqi Zhang, Hong Liu, Jinghua Pan, Yan Li, Danping Fan, Xinrong Fan.
      Prostate-related diseases, including prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer (PCa), represent significant threats to the health of the aging male population worldwide. Despite their prevalence, the pathogenesis of prostate-related diseases has not been elucidated. Recent studies have shown that N6-methyladenosine (m6A) modification is widely involved in the progression of prostate-related diseases. In this review, we summarized recent advances in understanding the core m6A regulatory machinery comprising writers such as the methyltransferase-like 3 (METTL3)-METTL14 complex, erasers including fat mass and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5), and readers, including the YTH domain-containing family proteins (YTHDFs), YTHDC proteins, insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs), and heterogeneous nuclear ribonucleoproteins (HNRNPs). Specifically, we elucidated how dysregulation of these components drives disease progression via alterations in cellular proliferation, differentiation, inflammatory responses, and stem cell dynamics. Notably, m6A modifications help shape the immunosuppressive landscape in PCa by modulating immune checkpoint expression, cytokine networks, and immune cell infiltration, thereby critically influencing therapeutic responses to immunotherapy. Furthermore, this review highlights the emerging diagnostic potential and therapeutic viability of m6A-targeted strategies, offering valuable insights for future clinical translation in prostate-related diseases.
    Keywords:  benign prostatic hyperplasia; m6A methylation modification; prostate cancer; prostate-related diseases; prostatitis
    DOI:  https://doi.org/10.3389/fimmu.2026.1685015
  30. Cell Host Microbe. 2026 Feb 27. pii: S1931-3128(26)00052-1. [Epub ahead of print]
    Immune activation reprograms growth mRNA stability to shape plant growth-defense trade-offs.
    Guilong Zhou, Ruixia Niu, Sitao Zhu, Hui Wang, Zhijuan Tang, Wanzhen Wang, Sirui Xiong, Jiawei Long, Yulu Zhou, Yongjia Tong, Hongchun Yang, Guoyong Xu.
      Immune activation enhances defense gene expression but often suppresses plant growth, creating a fundamental trade-off that limits durable resistance. While selective translation of defense mRNAs has been reported, how growth mRNAs are regulated after transcription during immune responses remains poorly understood. Here, using network-level analyses in Arabidopsis, we identify an RNA-binding protein-dependent mechanism that selectively destabilizes growth-related mRNAs upon immune activation. We show that polypyrimidine tract-binding protein 3 (PTBP3) recognizes a pyrimidine-rich RNA element, undergoes immune-induced condensation, and assembles an mRNA degradation hub that preferentially targets growth genes, including growth-regulating factors. Experimental disruption of this pathway-either by impairing PTBP3 function or by restoring growth gene expression-unexpectedly enhances disease resistance while improving growth resilience under immune stress. These findings reveal post-transcriptional control of growth mRNA stability as a regulatory layer shaping growth-defense balance and suggest a strategy for achieving stronger and safer plant immunity without constitutive defense activation.
    Keywords:  RNA degradation; RNA regulon; RNA-binding proteins; gene expression; growth mRNA; growth resilience; growth-defense trade-off; plant immune strategy; post-transcriptional control; translational control
    DOI:  https://doi.org/10.1016/j.chom.2026.02.007
  31. Front Immunol. 2026 ;17 1778481
    Decoding the role of RPL38 in lung adenocarcinoma: a multi-omics approach.
    Lu Zhang, Fei Teng, Yuan Wang, Yang Chen, Qiuxia Liu, Fengsheng Dai, Liang Yu, Chenguo Yao, Zhiqiang Wang.
       Introduction: Members of the Ribosomal Protein L (RPL) family are involved in diverse biological processes and cancer biology, yet their precise functions and clinical implications in lung adenocarcinoma (LUAD) remain incompletely understood.
    Methods: Machine learning was applied to The Cancer Genome Atlas (TCGA) data to identify pivotal RPL genes and construct a predictive risk model. Multi-omics analyses-including pan-cancer cohorts and spatial transcriptomics-were integrated to evaluate the expression and prognostic significance of Ribosomal Protein L38 (RPL38). Functional impacts were examined using CCK‑8, colony formation, wound healing, Transwell assays, and subcutaneous xenograft models.
    Results: A three‑gene RPL‑based prognostic signature was established from the TCGA‑LUAD cohort. High‑risk patients exhibited shorter survival and increased immunosuppressive characteristics. RPL38 was upregulated in multiple cancers and associated with unfavorable outcomes. Immunohistochemical and spatial transcriptomic analyses confirmed its aberrant expression in LUAD and linked it to an immunosuppressive tumor microenvironment. Genetic ablation of RPL38 significantly inhibited LUAD cell proliferation and migration in vitro, and impaired xenograft tumor growth in vivo.
    Conclusions: RPL38 plays a tumor‑promoting role in LUAD. This study clarifies the contribution of RPL38 to LUAD development, provides new insights into its pathogenesis, and suggests a rationale for therapeutic targeting of RPL38 in LUAD treatment.
    Keywords:  RPL38; lung adenocarcinoma; multi-omics data; progression; tumor immune; tumor microenvironment
    DOI:  https://doi.org/10.3389/fimmu.2026.1778481
  32. PLoS One. 2026 ;21(3): e0344276
    EpCAM silencing suppresses aggressive phenotypes and induces partial redifferentiation in anaplastic thyroid cancer cells.
    Teruo Nakamura, Tomohiro Shibata, Ken-Ichi Ito.
      Anaplastic thyroid cancer (ATC) is a rare but highly aggressive malignancy with a dismal prognosis. Although recent advances in targeted therapies have modestly improved survival, the molecular mechanisms driving ATC progression remain incompletely elucidated. Epithelial cell adhesion molecule (EpCAM), a multifunctional cell-surface protein, is implicated in proliferation, migration, and stemness in various cancers. However, its role in thyroid cancer progression remains unclear. In this study, we investigated the function of EpCAM in thyroid cancer cell lines of varying differentiation status. EpCAM expression was significantly elevated in ATC cell lines compared with differentiated thyroid cancer (DTC) lines. EpCAM knockdown by siRNA suppressed proliferation, adhesion, motility, and invasion in ATC cells, but had minimal effects on DTC cells. Morphological analyses revealed that EpCAM silencing induced differentiation features, including follicle-like structure formation and increased expression of thyroid differentiation markers such as thyroglobulin and PAX8 in ATC cells. Furthermore, EpCAM inhibition decreased mesenchymal marker expression, reduced filopodia formation, and suppressed extravasation of cancer cells into the lung in an in vivo mouse model. Mechanistically, EpCAM knockdown attenuated epithelial-mesenchymal transition (EMT)-related pathways but did not affect major proliferation signaling cascades in ATC cells. These findings suggest that EpCAM promotes dedifferentiation and metastatic potential in ATC through EMT modulation. Our results provide new insights into the role of EpCAM in thyroid cancer biology and highlight its potential as a therapeutic target in ATC. Further studies are warranted to elucidate the mechanisms linking EpCAM to anaplastic transformation and to explore the therapeutic efficacy of EpCAM-targeting strategies in aggressive thyroid cancers.
    DOI:  https://doi.org/10.1371/journal.pone.0344276
  33. Biochem J. 2026 Mar 04. 483(3): 375-389
    Structural and mechanistic basis of mTORC2 activation of protein kinase AKT/PKB.
    Nam Chu, Nhat Le, Ouada Nebie, Sammi Yang.
      The PI3K/AKT/mTOR signaling pathway is crucial for regulating essential cellular processes such as growth, survival, metabolism, and protein synthesis. Dysregulation of this pathway is strongly associated with diseases like cancer, where it drives uncontrolled cell proliferation and survival. The mTOR kinase forms two multiprotein complexes, mTORC1 and mTORC2, which govern distinct signaling pathways. mTORC1, regulated by nutrients, controls protein synthesis, cell growth, and autophagy, while mTORC2 acts as a central node in phosphoinositide 3-kinase (PI3K) and Ras signaling, often disrupted in cancer and diabetes. AKT, recruited by PIP3 to the plasma membrane, is phosphorylated by PDK1 and mTORC2, enabling it to regulate various cellular functions. Notably, mTORC2 selectively phosphorylates AKT and PKC but no other closely related kinases targeted by mTORC1, reflecting a high degree of substrate specificity. This specificity is due to structural elements in AKT that interact with the mTORC2 subunit mSin1 as revealed by recent studies using semisynthetic probes, paving the way for the design of mTORC2-specific inhibitors. Given the pathway's significant role in disease progression, particularly cancer, targeting the AKT/mTOR axis holds considerable therapeutic promise. However, challenges remain due to the complex regulation and feedback mechanisms in this pathway. Emerging combination therapies show promise in overcoming these obstacles. This review highlights the intricate regulation of the AKT/mTOR pathway and its potential for developing targeted therapies.
    Keywords:  AKT; cell signaling; mTOR; posttranslational modifications; protein kinase
    DOI:  https://doi.org/10.1042/BCJ20253108
  34. Mol Med Rep. 2026 May;pii: 129. [Epub ahead of print]33(5):
    Long non‑coding RNA NKILA regulates the JAK2/STAT3 pathway to exacerbate TGF‑β1‑mediated renal fibrosis.
    Yu Han, Siqi Yang, Jing Zhang, Yaoguang Wang, Xi Zhao, Huan Liu.
      Renal interstitial fibrosis is a common pathological outcome of acute and chronic kidney disease. Within the present study, the aim was to explore whether long non‑coding RNA (lncRNA) NKILA regulates TGF‑β1‑induced renal tubular epithelial fibrosis through the JAK‑2/STAT3 pathway and its underlying mechanisms. A renal fibrosis model was established by treating HK‑2 cells with TGF‑β1. RNA sequencing revealed marked dysregulation of the cis‑regulated lncRNA NKILA, associated with the JAK2/STAT3 pathway. Functional studies involved overexpressing NKILA using lentivirus in HK‑2 cells with TGF‑β1‑treated cells as a control and knocking it down in the fibrotic model. The JAK2 inhibitor AG490 was employed for rescue experiments. Protein and mRNA levels of epithelial‑mesenchymal transition (EMT) markers [fibronectin, collagen I, epithelial (E)‑cadherin, α‑smooth muscle actin and vimentin] and JAK2/STAT3 pathway components were assessed using western blotting, immunofluorescence and reverse transcription‑quantitative PCR. Findings revealed that lncRNA NKILA overexpression promoted fibrosis of TGF‑β1‑treated HK‑2 cells by activating the JAK2/STAT3 pathway. While knockdown of lncRNA NKILA alleviated the TGF‑β1‑induced EMT damage in HK‑2 cells, downregulated EMT markers and upregulated E‑cadherin expression by suppressing the activation of the JAK2/STAT3 pathway. Of note, AG490 prevented the damaging effects of lncRNA NKILA or TGF‑β1‑induced HK‑2 cells. Mechanistically, lncRNA NKILA promoted TGF‑β1‑induced renal injuries by activating the JAK2/STAT pathway. Overall, this suggests that lncRNA NKILA functions as an independent fibrogenic factor and affects the progression of renal interstitial fibrosis by regulating the JAK2/STAT3 signaling pathway.
    Keywords:  JAK2/STAT pathway; long non‑coding RNA NKILA; renal interstitial fibrosis
    DOI:  https://doi.org/10.3892/mmr.2026.13839
  35. Front Oncol. 2026 ;16 1741406
    RPL28 mediates sorafenib resistance in hepatocellular carcinoma by downregulating CDC6 expression.
    Yi Shi, Fangfang Chen, Yuanyuan Weng, Hang Zeng, Gang Chen.
       Aim: Sorafenib is a milestone targeted therapy for advanced hepatocellular carcinoma (HCC), yet resistance to this agent severely limits its clinical efficacy. The molecular mechanisms underlying sorafenib resistance are incompletely understood. Ribosomal proteins (RPs) have been increasingly implicated in cancer progression and drug resistance, but the role and mechanism of ribosomal protein L28 (RPL28) in sorafenib resistance in HCC remains unexplored.
    Methods: We investigated the functional role of RPL28 in sorafenib-resistant HCC using HepG2 and HCCLM3 cell models. RPL28 was silenced by siRNA, and effects on cell proliferation, migration, and sorafenib sensitivity were assessed by CCK-8, migration assays, and IC50 determination. Integrated transcriptomic and proteomic analyses were performed to delineate downstream pathways. The expression of immune-related proteins and key targets was validated by Western blotting.
    Results: RPL28 expression was significantly reduced at both mRNA and protein levels in knockdown cells of sorafenib-resistant HepG2 and HCCLM3. RPL28 knockdown inhibited proliferation and migration in resistant HCC cells. Transcriptomic and proteomic analyses identified CDC6 as a key downstream target of RPL28. CDC6 expression was consistently decreased in RPL28 KD cells, while EGFR and TRAF6 remained unchanged. GO and KEGG pathway enrichment revealed that RPL28 modulates pathways involved in DNA replication, immune regulation, and metabolic adaptation. Notably, no significant changes were observed in MHC-I and PD-L1 expression following RPL28 knockdown.
    Conclusions: Our findings demonstrate that RPL28 contributes to sorafenib resistance in HCC by upregulating CDC6, contributing to tumor proliferation and drug resistance. The newly identified RPL28-CDC6 axis represents a novel mechanism of resistance and a potential therapeutic target to overcome treatment limitations in HCC.
    Keywords:  CDC6; hepatocellular carcinoma; proteome; ribosomal proteins L28 (RPL28); sorafenib resistance; transcriptome
    DOI:  https://doi.org/10.3389/fonc.2026.1741406
  36. Mol Neurobiol. 2026 Mar 02. pii: 479. [Epub ahead of print]63(1):
    Granules Gone Rogue: Nuclear and Cytoplasmic Ribonucleoprotein Structures in Amyotrophic Lateral Sclerosis-Fused in Sarcoma (ALS-FUS) Pathology.
    Vanshika Ahuja, Bandana Sahu, Shiffali Khurana, Kritika Kumari, Nirmal Kumar Ganguly, Mandaville Gourie-Devi, Sagar Verma, Somasish G Dastidar, Vibha Taneja.
      Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the selective loss of motor neurons. Among its genetic subtypes, mutations in the fused in sarcoma (FUS) gene represent an aggressive form, often associated with early onset and rapid progression. FUS is a ubiquitously expressed DNA/RNA-binding nuclear protein involved in maintaining DNA damage repair and RNA metabolism. It also plays a crucial role in the formation of ribonucleoprotein (RNP) granules such as cytoplasmic stress granules and nuclear paraspeckles under stress. In ALS, pathogenic FUS mutations frequently disrupt the subcellular distribution of FUS, leading to cytoplasmic mislocalization and aggregation. Mutant FUS further disrupts granular dynamics by its aberrant incorporation into stress granules and altering their biophysical properties. The loss of nuclear FUS function leads to elevated levels of the long non-coding RNA NEAT1 and enhanced paraspeckle assembly with disrupted structural integrity. The impaired nucleocytoplasmic granular dynamics compromise the cellular resilience, thereby increasing motor neuron vulnerability. The interaction of FUS with other ALS-associated proteins causes pathological alterations in the cellular milieu, suggesting a common underlying disease mechanism. This comprehensive review emphasizes the FUS-mediated RNP granule regulation under physiological and pathological conditions. Further, clinically approved and emerging therapeutic strategies aimed at attenuating FUS pathology and RNP granule dynamics have been described.
    Keywords:  Amyotrophic lateral sclerosis; Fused in sarcoma; Paraspeckles; Ribonucleoprotein granules; Stress granules; Therapeutics
    DOI:  https://doi.org/10.1007/s12035-026-05736-9
  37. Cancer Genomics Proteomics. 2026 Mar-Apr;23(2):23(2): 210-219
    NPM1 Drives ERK1/2-dependent Tumor Progression in Lung Cancer.
    Hong-Beum Kim, Hee-Jeong Lee, Sang-Gon Park.
       BACKGROUND/AIM: Lung cancer is the most lethal malignancy worldwide, and there remains an urgent need for reliable biomarkers to improve diagnosis and treatment. Nucleophosmin 1 (NPM1), a nucleolar phosphoprotein, has been implicated in hematological cancers, but its significance in lung cancer is less clear. This study investigated the oncogenic role of NPM1 in lung cancer and its involvement in ERK1/2 pathway activation in lung cancer cells.
    MATERIALS AND METHODS: Transcriptomic data from TCGA were analyzed to assess NPM1 expression in lung cancer and normal tissues. In vitro assays using A549 and H1299 cells were conducted following siRNA-mediated silencing of NPM1. Cell proliferation, soft agar colony formation, and western blot analyses were performed. In vivo tumorigenicity was tested using a nude mouse xenograft model.
    RESULTS: NPM1 expression was significantly elevated in lung cancer tissues compared with normal samples. Silencing NPM1 reduced proliferation, colony formation, and tumor growth. Mechanistic studies revealed that NPM1 knockdown decreased phosphorylation of ERK1/2, indicating its role in activating this pathway.
    CONCLUSION: NPM1 contributes to lung cancer progression via ERK1/2 signaling. These results highlight NPM1 as a novel oncogene and suggest its potential as a diagnostic and prognostic biomarker in lung cancer.
    Keywords:  ERK1/2 signaling; Nucleophosmin 1 (NPM1); diagnostic biomarker; lung cancer; oncogene
    DOI:  https://doi.org/10.21873/cgp.20572
  38. Mol Cell Biol. 2026 Mar 02. 1-19
    Loss of Splicing Homeostasis as a Hallmark of Aging.
    Stefano Donega, Myriam Gorospe, Lorna W Harries, Luigi Ferrucci.
      Alternative splicing is a fundamental mechanism that ensures accurate gene expression, supports cellular adaptability, and expands protein diversity beyond the limits of a fixed gene pool. With aging, splicing fidelity weakens, contributing to decline in RNA homeostasis and disrupting essential cellular functions, including mitochondrial oxidative phosphorylation, genome stability, and immune regulation, and in turn accelerating tissue and organ dysfunction. Evidence from senescent cells, aged tissues, and model organisms shows that altered levels of splicing factors and increased RNA polymerase II elongation rates impair co-transcriptional splicing and promote mis-spliced isoforms that reinforce senescence and drive pathology. Dysfunction of RNA-binding proteins further contributes to aberrant splicing, linking splicing defects to age-related diseases such as atherosclerosis, osteoarthritis, sarcopenia, and neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Therapeutic strategies to correct splicing defects, such as antisense oligonucleotides, RNA interference, CRISPR-Cas systems, ADAR-mediated editing, and RNA aptamers, can restore a homeostatic balance of mRNA isoforms. However, major challenges remain, including distinguishing adaptive physiological from pathological splicing 'noise' and achieving targeted delivery to tissues. Despite these obstacles, RNA splicing dysregulation represents a promising avenue to extend health span by reestablishing homeostatic RNA programs, and reinforces the idea that "transcriptomic instability" is a hallmark of aging.
    Keywords:  Splicing; adaptive gene expression programs; aging; proteomic diversity; senescence
    DOI:  https://doi.org/10.1080/10985549.2026.2627235
  39. RNA Biol. 2026 Mar 06.
    5PSeq explorer: interactive analysis of Co-translational mRNA decay and ribosome dynamics.
    Irene Stevens, Vicent Pelechano.
       BACKGROUND: Co-translational mRNA decay occurs when 5'to 3' exonucleases follow the last translating ribosome, generating in vivo ribosome protected fragments. Degradome sequencing ;(5PSeq) therefore offers unique insights into ribosome dynamics. Despite its potential, resources for systematic analysis of 5'P mRNA decay intermediates and associated features, such as ribosome stalls and collisions, are scarce.
    FINDINGS: We introduce 5PSeq Explorer, a web-based platform built from 773 uniformly processed 5PSeq datasets across 23 species in bacteria and Ascomycota suitable for exploring ribosome dynamics in vivo at codon, amino acid, and transcript levels.
    CONCLUSIONS: By integrating normalized counts, structured metadata, and scalable visualization tools, 5PSeq Explorer provides a framework for studying the crosstalk between mRNA decay and ribosome dynamics. To ensure reproducibility and accessibility, we offer both a public web interface and a Docker-based plug-and-play local version.URL: https://fivepseq-explorer.serve.scilifelab.se/app/fivepseq-explorer.
    Keywords:  5PSeq; Ribosome dynamics; mRNA decay
    DOI:  https://doi.org/10.1080/15476286.2026.2639616
  40. Planta. 2026 Mar 04. pii: 90. [Epub ahead of print]263(4):
    The role of ubiquitination in regulating secondary metabolism in plants: mechanistic insights and biological significance.
    Kai Song, Zhijing Yu, Yashi Wen, Xiaoyu Xu, Jingying Liu, Mei Wang.
      Ubiquitination is a highly conserved and crucial post-translational modification that regulates protein turnover, signal transduction, and stress response in plants. Recent studies have shown that ubiquitination also plays a critical role in regulating secondary metabolism, a key factor in plant defense, environmental adaptation, and developmental transitions. By controlling the stability, activity, and regulatory functions of biosynthetic enzymes, transcription factors, and signaling molecules, ubiquitination dynamically influences metabolic flux and the accumulation of major classes of secondary metabolites. These changes, in turn, affect physiological processes such as the balance between growth and defense, resilience to biotic and abiotic stresses, and ecological interactions. This review consolidates current mechanistic insights into how ubiquitination governs the terpenoid, phenolic, and nitrogen-containing metabolic pathways, emphasizes the functional implications of these regulatory processes for plant performance, and outlines future research directions to link molecular mechanisms with metabolic outputs and plant-level phenotypes.
    Keywords:  Enzymes; Secondary metabolism; Signaling pathways; Transcription factors; Ubiquitination
    DOI:  https://doi.org/10.1007/s00425-026-04954-8
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