bims-micpro 2026-03-01 papers

bioRxiv. 2026 Feb 22. pii: 2026.02.21.707204. [Epub ahead of print]

HDAC5 -encoded Microprotein NISM Mediates Nucleolar Formation and Ribosomal RNA Synthesis.

Kevin Cao, Dat Ha, Jesse Hulahan, Lilianna Houston, Gregory Tong, Jiayi Weng, Natasha Huey, Hannah E DeMerit, Pedro Ortega, Rémi Buisson, Kingshuk Ghosh, Thomas F Martinez.

Ribosome biogenesis is the process by which ribosomal RNA (rRNA) and ribosomal proteins are synthesized, processed, and assembled into functional ribosomes. This process begins in the nucleolus, a multiphase liquid condensate. Here, we discover an arginine-rich disordered nucleolar microprotein encoded within the HDAC5 5'-UTR that we termed Nucleolar Integrity and Stress Microprotein (NISM). NISM overexpression leads to impaired rDNA transcription, triggering nucleolar stress, p53 activation, and suppressed proliferation. NISM knockout causes disruption of nucleolar structure and also induces p53 activation. Mechanistically, NISM interacts with the DExH-box RNA helicase DHX9 and regulates its activities related to pre-rRNA synthesis. Computational analyses and polymer physics-based mathematical modeling revealed that NISM coordinates nucleolar formation and pre-rRNA synthesis by enhancing the liquid-liquid phase separation of DHX9. This study establishes NISM as a regulator of nucleolar biology and deepens our understanding of how disordered microproteins can facilitate the formation of membraneless organelles.

DOI: https://doi.org/10.64898/2026.02.21.707204

Plant Biotechnol J. 2026 Feb 23.

Plant Peptides on the Rise: From Historical Insight to Future Applications.

Shunxi Wang, Jinghua Zhang, Minghui Chen, Bokai Zhang, Huina Zhao, Liuji Wu.

Plant peptides constitute a rapidly expanding class of signalling molecules essential to plant physiology, mediating key processes such as development, stress adaptation, and immune responses. This review traces the history of plant peptide research, from the seminal discovery of systemin to the recent identification of non-canonical peptides (NCPs) translated from small open reading frames (sORFs) in non-coding RNAs. We delineate the distinct biosynthetic pathways of canonical peptides (CPs), which undergo proteolytic processing and post-translational modifications, and NCPs, which are directly translated, often without further processing. The diverse biological functions of these peptides span development, reproduction, abiotic stress tolerance, biotic defence, and antimicrobial activity. Furthermore, we discuss emerging agricultural applications, including genetic engineering of peptides, exogenous peptide application, and trait optimization informed by natural peptide variation. Beyond agriculture, many plant peptides exhibit therapeutic potential due to their antimicrobial and anticancer properties. Despite significant advances, challenges remain in functional validation, field application, and scalable production. Future progress will depend on the integration of multi-omics approaches, artificial intelligence (AI)-driven prediction, and precision genome editing to fully harness the transformative potential of plant peptides for crop improvement and novel biopharmaceuticals.

Keywords: biomedicine; crop improvement; development; non‐canonical peptides; plant peptides; stress response

DOI: https://doi.org/10.1111/pbi.70613

Physiol Rep. 2026 Feb;14(4): e70791

Mitochondrial-derived peptides MOTS-c and humanin attenuate dexamethasone-induced atrophy in human skeletal muscle cells.

Rabie Elhusseiny, Mohammed Ihsan, Théo Bellefroid, Abdulaziz Farooq, Sébastien Racinais, Louise Deldicque.

Glucocorticoids, such as dexamethasone (DEXA), are effective therapeutics but cause severe muscle wasting. Mitochondrial-derived peptides (MDPs) are promising countermeasures, but their effectiveness is largely unexplored. We tested the hypothesis that the MDP S14G-humanin (HNG) and the mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) mitigate DEXA-induced atrophy in human skeletal myotubes. Fully differentiated primary human myotubes were exposed to 10 μM DEXA ±10 μM HNG or 10 μM MOTS-c. DEXA decreased myotube size (area, p < 0.001) and differentiation (Fusion Index, p = 0.05). Additionally, DEXA increased both muscle ring finger protein 1 (MURF1, p < 0.001) and muscle atrophy F-box (MAFbx, p = 0.01) as well as peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1α, p < 0.001). MOTS-c co-treatment with DEXA completely preserved myotube area (p < 0.001) and fusion index (p = 0.02), increased Akt phosphorylation (p = 0.0015) and blunted both MURF1 upregulation (p = 0.03) and STAT3 activation (p = 0.005) compared to DEXA alone. HNG co-treatment with DEXA preserved myotube area (p < 0.001), blunted DEXA-induced STAT3 activation (p = 0.027), but had no effect on fusion index or E3 ligase mRNA levels. Those findings suggest that MOTS-c could be an effective inhibitor of glucocorticoid-induced atrophy in human muscle, not only through selective inhibition of MURF1 but also by enhancing Akt signaling and suppressing STAT3 activation.

Keywords: atrogenes; fusion index; glucocorticoid; mitokines; myotubes

DOI: https://doi.org/10.14814/phy2.70791

bioRxiv. 2026 Feb 12. pii: 2026.02.11.705401. [Epub ahead of print]

The long noncoding RNA Malat1 contains an internal ribosome entry site mediating micropeptide translation.

Wen Xiao, Tanja Hann, Zion Perry, Vijaya Pandey, Jeffrey Cheng, James Wohlschlegel, Anna Marie Pyle, Douglas L Black.

In most cells, Malat1 long noncoding RNA localizes to the nucleus where it affects splicing and chromatin function. In neurons Malat1 is exported to the cytoplasm where it is translated to generate the M1 micropeptide. Here we characterize an internal ribosome entry site (IRES) required for Malat1 translation. Although preceded by a long Malat1 5' RNA segment this element induces translation at the M1 AUG. In vivo chemical probing and structural modeling identified a 135 nt RNA secondary structure consisting of three stem loops that is sufficient for IRES activity. Using this minimal element for affinity purification from cell extracts, the IRES RNA selectively binds ribosomal subunits and translation factors. Depletion of the binding proteins Rack1 and hnRNP A2/B1 inhibits downstream IRES-dependent translation without affecting translation of an upstream ORF. Our study identifies an unexpected functional unit hidden within a widely studied long noncoding RNA.

DOI: https://doi.org/10.64898/2026.02.11.705401

Cells. 2026 Feb 22. pii: 375. [Epub ahead of print]15(4):

LncRNA RORB-IT1 Encoding a Micropeptide Regulates Progesterone Synthesis, Proliferation and Apoptosis in Chicken Granulosa Cells.

Jie Cao, Qingqing Wei, Li Kang, Yi Sun, Yunliang Jiang.

Ovarian follicular development determines the egg-laying performance in chickens. Besides hormonal signaling, epigenetic and post-transcriptional regulators, long non-coding RNAs (lncRNAs) also play a vital role in follicular development. We previously identified that RAR-related orphan receptor B-intronic transcript 1 (RORB-IT1), a novel lncRNA located in the intron of RORB, was differentially expressed in chicken pre-hierarchical and hierarchical follicular granulosa cells (Post-GCs). However, it remains unknown whether RORB-IT1 participates in regulating the development of chicken ovarian follicles. In this study, we further characterized the expression pattern of RORB-IT1 and explored its role in regulating the progesterone synthesis, proliferation and apoptosis of chicken Post-GCs. The results showed that RORB-IT1, with a full length of 383 bp, exhibits a uniform distribution in both the cytoplasm and nucleus of chicken Post-GCs. RORB-IT1 was specifically expressed in Post-GCs and upregulated by follicle-stimulating hormone (FSH), progesterone (P4) and estradiol (E2) in a dose-dependent manner. Functionally, RORB-IT1 promoted P4 synthesis and proliferation, while inhibiting the apoptosis of Post-GCs. Furthermore, we demonstrated that RORB-IT1 encoded a functional micropeptide exhibiting dual localization in both cytoplasmic and nuclear compartments. This micropeptide enhanced progesterone synthesis and proliferation, but paradoxically induced the apoptosis of Post-GCs when overexpressed independently. Collectively, this study uncovered the expression pattern and function of RORB-IT1 in chicken Post-GCs and provided a theoretical basis for improving the egg-laying performance in chickens.

Keywords: LncRNA; RORB-IT1; chicken; granulosa cells; ovarian follicular development

DOI: https://doi.org/10.3390/cells15040375