bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2025–10–19
six papers selected by
Thomas Farid Martínez, University of California, Irvine
  1. Ribosome Profiling for Novel Antigen Discovery.
  2. Novel Insights Into Small Open Reading Frame-Encoded Micropeptides in Glioblastoma.
  3. RiboMicrobe: An Integrated Translatome Atlas for Microorganism.
  4. Bombyx mori nucleopolyhedrosis virus-derived circular RNAs with protein-coding potential facilitate viral replication.
  5. The organization principles of P. falciparum translation initiation features and their potential as drug targets.
  6. Insights into WDR5: unveiling its functions, regulation, and impact on skeletal muscle.
  1. Methods Mol Biol. 2026 ;2980 285-303
    Ribosome Profiling for Novel Antigen Discovery.
    Ana Xavier-Magalhães, Susan Klaeger.
      The identification of targetable antigens is crucial for advancing cancer immunotherapy. While traditional methods focus on tumor-associated antigens and somatic variants, recent advancements have highlighted novel antigen classes such as splice isoforms, gene fusions, ribonucleic acid (RNA) editing, and novel or unannotated open reading frames (nuORFs). These novel antigens offer promising targets due to their potential abundance and immunogenicity but are typically missed by traditional methods. Ribosome profiling (Ribo-seq) has emerged as a powerful technique for assessing and verifying translation of nuORFs that offer a plethora of novel targets. Mass spectrometry (MS)-based proteomics can validate the presence of translated proteins and peptides identified by Ribo-seq, providing direct evidence of protein expression and enhancing antigen discovery, potentially leading to the identification of novel cancer antigens for the development of more effective immunotherapies. This chapter explores the methodologies, challenges, and applications of Ribo-seq in combination with proteogenomic approaches for antigen discovery.
    Keywords:  Immunopeptidome; Mass spectrometry; NGS; Neoantigens; Novel or unannotated open reading frames (nuORFs); Proteogenomics; Ribo-seq; Tumor-associated antigens; Unannotated ORFs
    DOI:  https://doi.org/10.1007/978-1-0716-4832-2_13
  2. Cell Biol Int. 2025 Oct 15.
    Novel Insights Into Small Open Reading Frame-Encoded Micropeptides in Glioblastoma.
    Meiru Wang, Shuangshuang Pan, Jiaze Meng, Jiahong Jiang, Yajun Wang, Liu Yang.
      Glioblastoma is the most aggressive type of brain tumor, with a dismal prognosis, highlighting the urgent need for novel biomarkers and therapeutic targets. Recent advances in transcriptomics and proteomics have revealed the critical role of small open reading frame (sORF)-encoded micropeptides, a previously overlooked class of polypeptides derived from noncoding RNAs (ncRNAs), in glioblastoma pathogenesis. In this review, the current knowledge on the functional mechanisms of these micropeptides-including MP31, SHPRH-146aa, AKT3-174aa, and others-which regulate tumor metabolism, proliferation, angiogenesis, and therapeutic resistance, is synthesized. These micropeptides act as molecular switches by modulating key pathways or stabilizing tumor-suppressive proteins. We outline methods for identifying sORFs and validating their translation potential and functional characteristics. Emerging evidence highlights their diagnostic and prognostic value, as well as their therapeutic potential as peptide-based drugs or targets for precision oncology. Despite the challenges in detecting low-abundance micropeptides, their specificity and functional diversity make them promising candidates for improving glioblastoma management. Future studies should prioritize clinical translation and mechanistic exploration to harness their full potential in combating this lethal disease.
    Keywords:  functional mechanisms; glioblastoma; micropeptides; noncoding RNAs; small open reading frames
    DOI:  https://doi.org/10.1002/cbin.70093
  3. Adv Sci (Weinh). 2025 Oct 13. e09877
    RiboMicrobe: An Integrated Translatome Atlas for Microorganism.
    Yingshun Zhou, Jinjing Luo, Xiaoqiang Lang, Yuli Gan, Guoxian Liu, Yuling Cui, Fazhi Li, Weicong Zhu, Bing Chen, Yuanyuan Dong, Yinglin Wu, Yi Cao, Qi Liu.
      Ribosome profiling (Ribo-seq) represents a significant advance in translatomics research. This technique enables the precise measurement of global and in vivo translation dynamics, the quantification of translation, and the identification of active translated small open reading frames (sORFs). While several databases have been developed to focus on the translatome, comprehensive databases dedicated specifically to analyses of translation and sORFs in prokaryotes remain scarce. Therefore, RiboMicrobe (https://rnainformatics.org.cn/RiboMicrobe/ and https://rnainformatics.cn/RiboMicrobe/) develops a comprehensive database tailored for Ribo-seq data from prokaryotic microorganisms, Accompanying this database, it also introduces two novel sORF prediction models based on transformer-based deep learning architecture, sORFPredRibo and sORFPred, to support translatomics analyses and sORF annotation. Currently, RiboMicrobe encompasses 891 Ribo-seq, 369 matched RNA-seq, and 62 proteome datasets from 36 prokaryotes and 2 viruses, and provides users with intuitive web interfaces to easily access and explore information of interest. In addition, a suite of bioinformatics tools encompassing three functional categories: visualization tools (Browse, JBrowse, and mRNABrowse) is developed for data exploration; predictive algorithms (sORFPred and sORFPredRibo) for sORFs prediction; and comparative analysis utilities (DiffTE, DiffCO, and BLAST) for functional investigations. It is believed that the diverse data and capabilities of RiboMicrobe will advance the field of microbial translational research substantially.
    Keywords:  RiboMicrobe; prediction; prokaryotes; ribosome profiling; sORF; translatomics
    DOI:  https://doi.org/10.1002/advs.202509877
  4. Insect Biochem Mol Biol. 2025 Oct 09. pii: S0965-1748(25)00164-X. [Epub ahead of print]185 104420
    Bombyx mori nucleopolyhedrosis virus-derived circular RNAs with protein-coding potential facilitate viral replication.
    Xing Zhang, Zeen Shen, Yani Kang, Wenbin Yu, Xiaoyan Du, Qian Teng, Zihan He, Chengliang Gong, Xiaolong Hu.
      Circular RNAs (circRNAs) are renowned for their exceptional stability and have been increasingly recognized for their dual roles in pro- and antiviral responses during host-virus interactions. In this study, we investigated the functional landscape of circular RNAs (circRNAs) during infection with Bombyx mori nucleopolyhedrosis virus (BmNPV), a model baculovirus system. Our comprehensive analysis revealed that hundreds of host-derived circRNAs are dynamically regulated upon BmNPV infection, while the virus itself generates numerous viral circRNAs (vcircRNAs) via back-splicing. Using a combination of advanced experimental approaches, we validated the existence of multiple cellular and viral circRNAs. Among these, we characterized vcircRNA-390, a BmNPV-encoded circRNA harboring a small open reading frame (ORF) and four viral internal ribosome entry sites (IRESs). Remarkably, vcircRNA-390 serves as a template for the translation of an 81-amino acid viral peptide (VSP81). Functional studies demonstrated that both vcircRNA-390 and VSP81 significantly enhance viral replication. Mechanistically, we provide evidence that VSP81 likely targets the host RNA interference (RNAi) pathway, a major antiviral defence system, to promote viral immune evasion. While these findings establish vcircRNA-390 as a novel proviral factor in insect-virus interactions, the detailed molecular mechanisms by which VSP81 modulates the RNAi machinery remain to be fully elucidated. Our work not only expands the understanding of viral circRNA biology but also reveals a new dimension of the host-pathogen conflict, wherein BmNPV exploits circRNA-mediated translation to subvert antiviral defences.
    Keywords:  BmNPV; VSP81; Viral circRNA; Viral replication; vcircRNA-390
    DOI:  https://doi.org/10.1016/j.ibmb.2025.104420
  5. Nucleic Acids Res. 2025 Oct 14. pii: gkaf959. [Epub ahead of print]53(19):
    The organization principles of P. falciparum translation initiation features and their potential as drug targets.
    Rom Barzilay, Anastasia Lev, Davide Fraticelli, Ariel Ogran, Alicia Rojas, Paula Abou Karam, Neta Regev-Rudzki, Rivka Dikstein.
      Plasmodium (P.) falciparum, the deadliest malaria-causing parasite, challenges eradication efforts due to drug resistance. The regulation of mRNA translation as a therapeutic target remains unexplored. Most mRNAs contain unusually long 5'UTR and multiple upstream AUGs. How the parasite overcomes scanning distance and multiple uORF constraints is unknown. We employed the eIF1-eIF4G1 inhibitor i14G1-12, Ribo-seq, TIS-seq, and long-read data on P. falciparum trophozoites. Re-annotation of 5'UTRs, initiation site mapping, and translation efficiency (TE) analysis revealed extended 5'UTR length in hundreds of genes and actively translated uORFs in 81% of mRNAs. Active uORFs were predominantly initiated with AUG lacking specific context, while inactive uORFs were enriched with inhibitory AUG contexts. Notably, initiation within coding sequence through leaky scanning is also highly prevalent. Surprisingly, mRNAs with long 5'UTR and active uORFs exhibit higher TE than those without. We demonstrate that this is facilitated by a specific spacing of active uORFs and peptide length, optimizing scanning distance, ribosome density, and reinitiation. Remarkably, short-term i14G1-12 treatment reduced parasite viability and caused translational repression by enhancing leaky scanning and disturbing the unique arrangement of uORFs. Collectively, our findings uncovered the unusual translation regulatory features of P. falciparum and highlighted the therapeutic potential of targeting these mechanisms.
    DOI:  https://doi.org/10.1093/nar/gkaf959
  6. Epigenetics. 2025 Dec;20(1): 2573998
    Insights into WDR5: unveiling its functions, regulation, and impact on skeletal muscle.
    Erick Bahena-Culhuac, Mauricio Hernández-Somilleda, José Manuel Hernández-Hernández.
      WD40-repeat-containing protein 5 (WDR5) is a highly conserved multifunctional scaffold protein with a toroidal structure, facilitating interactions with numerous partners through its WDR5-binding motif (WBM) and WDR5-interacting (WIN) sites. It plays a critical role in histone modifications, including H3K4 methylation (H3K4me), histone acetylation, and deacetylation, influencing stem cell maintenance and differentiation. Recent studies highlight its involvement in muscle homeostasis, particularly in skeletal muscle progenitor cells, where it regulates PAX7-driven myogenic factor expression. Additionally, WDR5 governs epigenetic programs in smooth muscle by modulating H3K4me marks on lineage-specific genes. Despite extensive research on its role in cancer and chromatin remodeling, its broader physiological functions remain underexplored. This review examines WDR5's regulatory mechanisms, including its modulation by long non-coding RNAs (lncRNAs), post-translational modifications (PTMs), and microproteins, while emphasizing its relevance to muscle biology. Understanding WDR5's interactome and regulatory networks could provide novel insights into muscle regeneration, stem cell dynamics, and potential therapeutic strategies for muscular disorders and regenerative medicine.
    Keywords:  WDR5; chromatin remodeling; epigenetics; histone modifications; muscle regeneration
    DOI:  https://doi.org/10.1080/15592294.2025.2573998
This page is being maintained by Thomas Krichel. It was last updated on 2025‒11‒18 at 23:52.