bims-mirnam 2026-01-04 papers

bims-mirnam

Biomed News

on Mitochondrial RNA metabolism

Issue of 2026–01–04
fourteen papers selected by
Hana Antonicka, McGill University

Advances in Detecting RNA Modifications Using Direct RNA Nanopore Sequencing.
Advances in Quantitative Techniques for Mapping RNA Modifications.
RBProximity-CLIP Enables Subcellular Mapping of RNA-Binding Protein Interactions at Nucleotide Resolution.
Mitochondrial tRNA-Derived Diseases.
Self-renewal of neuronal mitochondria through asymmetric division.
RNA modifications: roles in immune cell biology and tumor regulation.
Predicting small molecule-RNA interactions without RNA tertiary structures.
Synthetic Pentatricopeptide Repeat Proteins: Building a Toolkit for Precise RNA Control.
Reconnaissance of the Good, the Bad, and the Ugly Role of tRNAs in Carcinogenesis and Metastasis.
Differential expression of mitomiRs in pancreatic islet cells associated with maternal protein restriction.
Flexizyme-Based Strategy for the Synthesis of Stable, Non-Isomerizable Amide-Linked 2'-Aminoacyl-tRNAs and their Shortened Analogs.
Nsun2-mediated m5C methylation of Ncor1 exacerbates sepsis-induced cardiomyopathy by promoting mitochondrial dysfunction.
DEAD-box ATPase-marked condensates coordinate compartmentalized translation and antibiotic persistence.
R-loops and small RNA regulatory interactions: mechanisms and clinical perspectives.

Adv Genet (Hoboken). 2025 Dec;6(4): e00041

Advances in Detecting RNA Modifications Using Direct RNA Nanopore Sequencing.

Yaran Liu, Yang Li, Qiang Sun.

  RNA modifications add a dynamic and versatile regulatory layer to gene expression, influencing RNA stability, splicing, translation, and cellular responses. Despite their importance, traditional detection methods-such as antibody-based enrichment, chemical labeling, or indirect sequencing approaches-often suffer from limited resolution, biases, and an inability to capture modifications in their native RNA context. Oxford Nanopore Technologies (ONT) direct RNA sequencing (DRS) overcomes many of these limitations by enabling amplification-free, single-molecule, and single-nucleotide detection of diverse RNA modifications directly from native RNA molecules. In this review, recent advances in applying ONT DRS to characterize modifications beyond the extensively studied N6-methyladenosine (m6A), including 2'-O-methylation (Nm), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N4-acetylcytidine (ac4C), N7-methylguanosine (m7G), pseudouridine (Ψ), and adenosine-to-inosine (A-to-I) editing are summarized. Computational frameworks and basecalling innovations are highlighted that improve modification calling, with particular emphasis on approaches that detect co-occurring modifications and reveal their potential regulatory cross-talk within individual transcripts. Finally, emerging applications across synthetic systems, non-model organisms, and disease contexts are discussed, and offer a forward-looking perspective on integrating nanopore-based epitranscriptomics with multi-omics platforms to achieve a deeper and more comprehensive understanding of RNA regulation.

Keywords:  Oxford Nanopore Technologies; RNA modifications; direct RNA sequencing; epitranscriptomics; single‐molecule analysis

DOI:  https://doi.org/10.1002/ggn2.202500041
Life (Basel). 2025 Dec 10. pii: 1888. [Epub ahead of print]15(12):

Advances in Quantitative Techniques for Mapping RNA Modifications.

Ling Tian, Bharathi Vallabhaneni, Yie-Hwa Chang.

  RNA modifications are essential regulators of gene expression and cellular function, modulating RNA stability, splicing, translation, and localization. Dysregulation of these modifications has been linked to cancer, neurodegenerative disorders, viral infections, and other diseases. Precise quantification and mapping of RNA modifications are crucial for understanding their biological roles. This review summarizes current and emerging methodologies for RNA modification analysis, including mass spectrometry, antibody-based and non-antibody-based approaches, PCR- and NMR-based detection, chemical- and enzyme-assisted sequencing, and nanopore direct RNA sequencing. We also highlight advanced techniques for single-cell and single-molecule imaging, enabling the study of modification dynamics and cellular heterogeneity. The advantages, limitations, and challenges of each method are discussed, providing a framework for selecting appropriate analytical strategies. Future perspectives emphasize high-throughput, multiplexed, and single-cell approaches, integrating multiple technologies to decode the epitranscriptome. These approaches form a robust toolkit for uncovering RNA modification functions, discovering biomarkers, and developing novel therapeutic strategies.

Keywords:  RNA modifications; biomarker discovery; chemical-assisted sequencing; epitranscriptomics; mass spectrometry; nanopore direct RNA sequencing; single-cell analysis; single-molecule imaging

DOI:  https://doi.org/10.3390/life15121888
bioRxiv. 2025 Dec 15. pii: 2025.12.12.693770. [Epub ahead of print]

RBProximity-CLIP Enables Subcellular Mapping of RNA-Binding Protein Interactions at Nucleotide Resolution.

Iwona Nowak, Ahsan H Polash, Hang T Huynh, Mahekdeep Kaur, Vivian Lobo, Jérémy Scutenaire, Michelle Fong, Ghaliah Alluhaibi, Dimitrios G Anastasakis, Markus Hafner, Daniel Benhalevy, Aishe A Sarshad.

RNA-binding proteins (RBPs) enable post-transcriptional gene regulation (PTGR) through specific interactions with RNA molecules, influencing processes ranging from nuclear processing and export to cytoplasmic localization, translation, storage and degradation. A key determinant of PTGR processes is the subcellular compartmentalization of RBPs, which dictates RNA targets they can access and the regulation performed in that environment. To characterize RBP-RNA interactions at subcellular resolution, we developed RBProximity-CLIP. RBProximity-CLIP enables compartment-specific isolation and profiling of individual RBP-RNA interactions by combining APEX2-based proximity labeling and 4-thiouridine-enhanced RNA-protein crosslinking, with sequential RBP- and biotin-affinity purifications. Using this approach, we profiled the RNA targets of three RBPs, AGO2, YBX1, and ELAVL1, across the cytoplasmic, nuclear, and nucleolar compartments, revealing nucleus-specific miRNA-mediated AGO2 targets, as well as subsets of YBX1 and ELAVL1 targets that differ by compartment, yet share identical binding motifs. RBProximity-CLIP enables specific and sensitive detection of compartment-specific RBP-RNA interactomes, thereby providing new insight into spatial gene regulation by RBPs.

DOI: https://doi.org/10.64898/2025.12.12.693770
Int J Mol Sci. 2025 Dec 13. pii: 12023. [Epub ahead of print]26(24):

Mitochondrial tRNA-Derived Diseases.

Antonia Petropoulou, Nikolaos Kypraios, Dimitra Rizopoulou, Adamantia Kouvela, Alexandros Maniatis, Katerina Anastasopoulou, Alexandra Anastogianni, Theodoros Korfiatis, Katerina Grafanaki, Vassiliki Stamatopoulou, Constantinos Stathopoulos.

  Mitochondrial tRNA genes are critical hotspots for pathogenic mutations and several mitochondrial diseases. They account for approximately 70-75% of disease-causing mtDNA variants despite comprising only 5-10% of the mitochondrial genome. These mutations interfere with mitochondrial translation and affect oxidative phosphorylation, resulting in remarkably heterogeneous multisystem disorders. Under this light, we systematically reviewed PubMed, Scopus, and MITOMAP databases through October 2025, indexing all clinically relevant pathogenic mt-tRNA mutations classified by affected organ systems and underlying molecular mechanisms. Approximately 500 distinct pathogenic variants were identified across all 22 mt-tRNA genes. Beyond typical syndromes like MELAS, MERRF, Leigh syndrome, and Kearns-Sayre syndrome that are linked to mt-tRNA mutations, they increasingly implicate cardiovascular diseases (cardiomyopathy, hypertension), neuromuscular disorders (myopathies, encephalopathies), sensory impairment (hearing loss, optic neuropathy), metabolic dysfunction (diabetes, polycystic ovary syndrome), renal disease, neuropsychiatric conditions, and cancer. Beyond sequence mutations, defects in post-transcriptional modification systems emerge as critical disease mechanisms affecting mt-tRNA function and stability. The mutations on tRNA genes described herein represent potential targets for emerging genome editing therapies, although several translational challenges remain. However, targeted correction of pathogenic mt-tRNA mutations holds transformative potential for precision intervention on mitochondrial diseases.

Keywords:  human diseases; mitochondrial tRNA; mt-tRNA modifications; mtDNA mutations

DOI:  https://doi.org/10.3390/ijms262412023
bioRxiv. 2025 Dec 18. pii: 2025.12.17.694973. [Epub ahead of print]

Self-renewal of neuronal mitochondria through asymmetric division.

Tejashree Pradip Waingankar, Camryn Zurita, Angelica E Lang, Cliff Vuong, Ahmad Shami, Diana Bautista, Catherine Drerup, Samantha C Lewis.

Mitochondrial ATP production is essential for life. Mitochondrial function depends on the spatio-temporal coordination of nuclear and mitochondrial genome expression, yet how this coordination occurs in highly polarized cells such as neurons remains poorly understood. Using high-resolution imaging in mouse peripheral sensory neurons and zebrafish larvae, we identified a sub-population of mitochondria enriched in mtDNA that are positioned at the collateral branch points of long sensory neurites, both in vitro and in vivo . While the mitochondria in neurites are generally depleted of mtDNA, those at axon branch points preferentially engage in mtDNA replication and transcription, accumulate nuclear-encoded mitochondrial mRNA, and are spatially linked to nascent cytosolic peptide synthesis. The mtDNA-positive mitochondrial pool exhibits asymmetric genome partitioning at division, shedding highly motile daughters that lack mtDNA. Asymmetric division rejuvenates the membrane potential of the mtDNA-rich, biogenesis-dedicated mitochondria. We also found that, in peripheral sensory neurons, axonal mitochondria rarely fuse or share matrix contents, explaining how differentiated daughters maintain their distinct composition and fate after fission. Thus, division-coupled mitochondrial self-renewal is yoked to neurite topology in sensory neurons, patterning mitochondrial diversity and homeostasis from micron to meter scales.

DOI: https://doi.org/10.64898/2025.12.17.694973
Cancer Cell Int. 2025 Dec 28.

RNA modifications: roles in immune cell biology and tumor regulation.

Hongyan Liu, Zihan Yang, Ziyi Xu, Xiaochen Ding, Xue Chen, Penghui Li, Jiachun Sun.

  In recent years, RNA modifications have been shown to play a key role in regulating immune cell functions, reshaping the tumor immune microenvironment (TIME), mediating immune escape, and influencing the efficacy of immunotherapy. These processes are central to the field of epitranscriptomics. Researchers have discovered various RNA modifications, such as N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m¹A), N7-methylguanosine (m7G), and N4-acetylcytosine (ac4C), that dynamically regulate the development, differentiation, activation, and functional state of immune cells through the " writers-readers-erasers " system-a set of enzymes that add, recognize, and remove these modifications-thus contributing to the formation and evolution of the TIME. Furthermore, RNA modification enzymes can serve as predictive markers of general immune responses and are also closely linked to responses to immunotherapy. Accordingly, they have become potential targets for combination therapies. As RNA modification detection technologies advance, researchers are uncovering the spatial heterogeneity and cell-specific regulatory mechanisms of RNA modifications in tumor immunity, which provides new strategies for targeted immunotherapy. However, the regulatory mechanisms of certain RNA modifications on specific immune cells remain unclear, and how to translate research findings into clinical applications also requires further exploration.

Keywords:  Cancer; Immune cells; Immunotherapy; RNA modifications; Tumor immunity

DOI:  https://doi.org/10.1186/s12935-025-04096-z
Nat Biotechnol. 2026 Jan 02.

Predicting small molecule-RNA interactions without RNA tertiary structures.

Yuhan Fei, Pengfei Wang, Jiasheng Zhang, Xinyue Shan, Zilin Cai, Jianbo Ma, Yangming Wang, Qiangfeng Cliff Zhang.

Small molecules can bind RNAs to regulate their fate and functions, providing promising opportunities for treating human diseases. However, current tools for predicting small molecule-RNA interactions (SRIs) require prior knowledge of RNA tertiary structures. Here we present SMRTnet, a deep learning method that uses multimodal data fusion to integrate two large language models with convolutional and graph attention networks to predict SRIs on the basis of RNA secondary structure. SMRTnet achieves high performance across multiple experimental benchmarks, substantially outperforming existing tools. SMRTnet predictions for ten disease-associated RNA targets identified 40 hits of RNA-targeting small molecules with nanomolar-to-micromolar dissociation constants. Focusing on the MYC internal ribosome entry site, SMRTnet-predicted small molecules showed binding scores correlated closely with observed validation rates. One predicted small molecule downregulated MYC expression, inhibited proliferation and promoted apoptosis in three cancer cell lines. Thus, by eliminating the need for RNA tertiary structures, SMRTnet expands the scope of feasible RNA targets and accelerates the discovery of RNA-targeting therapeutics.

DOI: https://doi.org/10.1038/s41587-025-02942-z
Int J Mol Sci. 2025 Dec 14. pii: 12033. [Epub ahead of print]26(24):

Synthetic Pentatricopeptide Repeat Proteins: Building a Toolkit for Precise RNA Control.

Jose M Lombana, Maureen R Hanson, Stephane Bentolila.

  In plants, cytidine-to-uridine (C-to-U) and uridine-to-cytidine (U-to-C) editing events are directed by pentatricopeptide repeat (PPR) proteins, modular RNA-binding factors that recognize their RNA targets through a predictable amino acid-nucleotide recognition code. Deciphering this code has enabled the rational design of synthetic PPR (synPPR) proteins with programmable RNA-binding specificity and robust stability in heterologous systems. Recent advances have extended these synthetic scaffolds to active RNA editors by fusing them to catalytically competent DYW deaminase domains, generating customizable enzymes capable of precise base conversion in bacteria, plants, and even human cells. This review summarizes current understanding of the structural and mechanistic principles underlying PPR-mediated RNA editing and highlights recent progress in the design and application of synPPR proteins. We discuss how synthetic PPR proteins have been used as programmable RNA stabilizers, translational regulators, and targeted C-to-U or U-to-C editors, as well as their emerging therapeutic potential in RNA-mediated diseases. The development of compact, cofactor-independent editors derived from early-diverging plant lineages further expands the versatility of this platform. Together, these efforts establish synthetic PPR proteins as a powerful and flexible class of RNA engineering tools with applications spanning basic research, biotechnology, and biomedicine. Continued refinement of targeting specificity, catalytic efficiency, and effector modularity will propel PPR-based editors toward broader use in synthetic biology and therapeutic RNA modulation.

Keywords:  RNA editing; RNA engineering; pentatricopeptide repeat (PPR) proteins; programmable RNA recognition; synthetic biology

DOI:  https://doi.org/10.3390/ijms262412033
Exp Suppl. 2026 ;115 111-122

Reconnaissance of the Good, the Bad, and the Ugly Role of tRNAs in Carcinogenesis and Metastasis.

Malik Ali Asghar, Mehraj Abbasov, Rukset Attar, Ammad Ahmad Farooqi.

  Our current knowledge of the translational mechanisms and the detailed structural insights of its components have highlighted the characteristically exclusive role of tRNAs and aminoacyl-tRNA synthetase diversity in the evolution of the genetic codes. Phenomenal advancements in mass spectrometry and high-throughput sequencing have enabled the researchers in developing a better understanding of the complex landscape of tRNA modifications. Emerging evidence has started to shed light on linchpin role of tRNAs in carcinogenesis and metastatic dissemination. In this chapter, we have provided an overview of the role of tRNAs, aminoacyl-tRNA synthetases, and tRNA-derived small RNAs in the onset and progression of cancer.

Keywords:  Carcinogenesis; Metastasis; Noncoding RNA; tRNAs

DOI:  https://doi.org/10.1007/978-3-032-06948-1_4
Islets. 2026 Dec 31. 18(1): 2610590

Differential expression of mitomiRs in pancreatic islet cells associated with maternal protein restriction.

Cecile Jacovetti, Romano Regazzi.

   OBJECTIVE: Mitochondria are central to energy production and cellular homeostasis. Beyond importing diverse RNAs, they also encode hundreds of their own non-coding RNAs, contributing to a complex and dynamic RNA landscape. Early-life nutritional insults, such as fetal and postnatal protein deficiency, can impair mitochondrial function and increase the long-term diabetes risk. However, the mitochondrial non-coding transcriptome of pancreatic islets, particularly its responsiveness to nutritional cues, remains largely unexplored.
METHODS: We performed RNA sequencing to profile small non-coding RNAs in mitochondrial fractions of islet cells from offspring of rats exposed to low-protein (LP) or control diets during gestation and lactation and employed mRNA-miRNA network analysis to explore the potential regulatory roles of differentially expressed mitomiRs in LP-exposed pups.
RESULTS: Protein deficiency during gestation and lactation led to a profound remodeling of the small non-coding RNA landscape in whole islets, with microRNAs and piRNAs showing the most pronounced changes. In mitochondrial fractions, LP exposure resulted in a striking shift in microRNA composition, with 33 mitomiRs detected in control islets versus 23 in LP-exposed rats, and only 5 shared between groups. Notably, ten mitomiRs were selectively depleted from the cytosol and enriched in mitochondria of LP-exposed islets. Amongst these, miR-10a-5p and miR-126a-5p, are predicted to target genes involved in mitochondrial metabolism and structural organization.
CONCLUSION: Early-life protein restriction triggers a highly selective reorganization of the mitomiR landscape in pancreatic islets. The identified mitomiRs may serve as regulators of mitochondrial function and intracellular signaling, potentially influencing β-cell metabolic coupling and contributing to diabetes susceptibility.

Keywords:  Diabetes susceptibility; Mitochondrial non-coding transcriptome; Small non-coding RNAs; mitomiRs

DOI:  https://doi.org/10.1080/19382014.2025.2610590
Chemistry. 2025 Dec 30. e03506

Flexizyme-Based Strategy for the Synthesis of Stable, Non-Isomerizable Amide-Linked 2'-Aminoacyl-tRNAs and their Shortened Analogs.

Lia Maurin, Carine Tellier-Lebegue, Laura Iannazzo, Takayuki Katoh, Delphine Patin, Vincent Guerineau, Mélanie Ethève-Quelquejeu, Muriel Gondry, Matthieu Fonvielle.

  The study of the regiospecificity of aminoacyl-tRNA (AA-tRNA)-dependent enzymes and their structural characterization with AA-tRNAs are limited by rapid hydrolysis of the ester bond linking amino acid to tRNA. To overcome this limitation, stable AA-tRNA analogs bearing hydrolysis-resistant linkages, such as amide bonds or ester bioisosteres, have been developed. These analogs are valuable tools for investigating interactions between AA-tRNAs and various enzymes or ribonucleoproteins, including elongation factors, ribosomes, Fem-family transferases, and cyclodipeptide synthases. However, their synthesis remains technically challenging. Recently, flexizymes-engineered ribozymes capable of aminoacylating tRNAs with diverse amino acids or analogs-have enabled the synthesis of 3'-amide-linked AA-NH-tRNAs. Due to their inherent specificity for 3'-OH acylation, flexizymes have not been used to generate 2'-amide-linked analogs, and such regioisomers have remained unexplored. In this study, we demonstrate that while flexizymes cannot directly aminoacylate the 2' position, they can nevertheless mediate the synthesis of 2'-aminoacyl-NH-tRNAs via a two-step regioisomerization mechanism with excellent yields. This finding provides new insights into the binding mode of AA-tRNAs to flexizymes and expands the chemical space of stable AA-tRNA analogs. Access to both 3'- and 2'-amide regioisomers will enable more precise studies of AA-tRNA recognition and catalysis by various AA-tRNA-dependent systems.

Keywords:  2’‐aminoacyl‐NH‐tRNA; 3’‐aminoacyl‐NH‐tRNA; Fem transferase; Staphylococcus aureus; flexizyme

DOI:  https://doi.org/10.1002/chem.202503506
Free Radic Biol Med. 2025 Dec 30. pii: S0891-5849(25)01474-1. [Epub ahead of print]

Nsun2-mediated m5C methylation of Ncor1 exacerbates sepsis-induced cardiomyopathy by promoting mitochondrial dysfunction.

Chan Chen, Qing Liu, Junmei Xu, Mengyuan Zi, Xinglan Chen, Feng Xiao.

  Sepsis-induced cardiomyopathy (SIC) is a severe complication of sepsis characterized by mitochondrial dysfunction and impaired myocardial contractility, yet its molecular pathogenesis remains incompletely understood. In this study, we demonstrate that excessive mitochondrial fission plays a pivotal role in SIC, contributing to inflammation, oxidative stress, and cardiomyocyte apoptosis. Pharmacological inhibition of mitochondrial fission using Mdivi-1 alleviated these pathological changes both in vivo and in vitro. Bioinformatic analyses of public datasets identified nuclear receptor corepressor 1 (Ncor1) as a key mitochondrial dynamics-related gene upregulated in SIC. Lentiviral knockdown of Ncor1 mitigated myocardial injury and restored mitochondrial homeostasis in both lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) induced SIC mouse model. Mechanistically, we found that the RNA m5C methyltransferase Nsun2 was significantly upregulated in SIC and enhanced Ncor1 mRNA stability via m5C methylation through reading protein ALYREF. Functional experiments revealed that Nsun2 knockdown ameliorated cardiomyocyte injury, while co-knockdown of Ncor1 reversed the deleterious effects of Nsun2 overexpression. Collectively, our findings reveal a novel Nsun2/Ncor1 axis that drives mitochondrial dysfunction in SIC through epi transcriptomic regulation, providing potential therapeutic targets for septic cardiac injury.

Keywords:  Cardiomyocyte apoptosis; Mitochondrial fission; Ncor1; Nsun2; Sepsis-induced cardiomyopathy (SIC); m5C RNA methylation

DOI:  https://doi.org/10.1016/j.freeradbiomed.2025.12.056
Sci Adv. 2026 Jan 02. 12(1): eady1930

DEAD-box ATPase-marked condensates coordinate compartmentalized translation and antibiotic persistence.

Ziyin Zhang, Daqian Li, Bo Zheng, Jia-Feng Liu.

Antibiotic-tolerant persisters use dormancy as a bet-hedging strategy to evade lethal antibiotics, undermining therapeutic efficacy. Protein condensates have been implicated in bacterial dormancy, yet how these assemblies orchestrate dormancy entry remains unclear. We evolved persisters that enter dormancy before the stationary phase, most harboring mutations in serS, encoding seryl-transfer RNA synthetase (SerRS). These variants recapitulated persistence induced by serine hydroxamate (SHX), a serine analog and SerRS inhibitor. Both the serS mutation and SHX treatment trigger SerRS sequestration into conserved DEAD-box adenosine triphosphatase-associated condensates, coinciding with growth arrest and dormancy. In vitro, the SerRS variant preferentially partitions into DeaD granules, consistent with its distinct in vivo localization. Microscopy revealed spatially restricted translation silencing within condensates upon SerRS partitioning. Together, these phase-separated condensates act as hubs that coordinate the transition from proliferation to dormancy, paralleling eukaryotic cell fate control via localized translation. Our findings provide mechanistic insight into bacterial persistence and suggest that targeting condensates could help combat antibiotic tolerance and delay resistance.

DOI: https://doi.org/10.1126/sciadv.ady1930
Front Cell Dev Biol. 2025 ;13 1727548

R-loops and small RNA regulatory interactions: mechanisms and clinical perspectives.

Si-Yao Wang, Ya-Ni Liu, Si-Qiao Zhao, Wen Liu, Jin-Long Hu, Fan Yang, Sheng Wang.

  An R-loop is a three-stranded nucleic acid structure that serves as a transcriptional intermediate, consisting of an RNA-DNA hybrid and a displaced single-stranded DNA (ssDNA). Small RNAs are RNA molecules shorter than 300 nucleotides that perform a wide range of essential functions within cells. Both R-loops and small RNAs are widely present in the genomes of prokaryotes and eukaryotes, where they play crucial roles in regulating gene expression, maintaining genomic stability, and facilitating DNA damage repair. Aberrant formation and accumulation of R-loops, coupled with dysregulation of small RNA pathways, can induce DNA damage and genomic instability, ultimately contributing to cellular senescence or cell death. Here, we discuss recent advances in understanding the crosstalk between R-loops and small RNAs, with a focus on their synergistic roles in maintaining genome stability and their therapeutic potential in oncology and neurodegeneration. We propose a novel model integrating R-loop dynamics with small RNA-mediated epigenetic regulation, supported by emerging clinical trial data.

Keywords:  DNA repair; R-loops; RNA-DNA hybrids; genomic instability; small RNAs; transposon silencing

DOI:  https://doi.org/10.3389/fcell.2025.1727548