bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2025–04–27
six papers selected by
Thomas Farid Martínez, University of California, Irvine
  1. Bakta Web - rapid and standardized genome annotation on scalable infrastructures.
  2. From non-coding RNAs to cancer regulators: The fascinating world of micropeptides.
  3. The implication of non-AUG-initiated N-terminally extended proteoforms in cancer.
  4. Endogenous micropeptides as potential diagnostic biomarkers and therapeutic drugs.
  5. Morphogenesis, starvation, and light responses in a mushroom-forming fungus revealed by long-read sequencing and extensive expression profiling.
  6. Popcorn: prediction of short coding and noncoding genomic sequences in prokaryotes.
  1. Nucleic Acids Res. 2025 Apr 24. pii: gkaf335. [Epub ahead of print]
    Bakta Web - rapid and standardized genome annotation on scalable infrastructures.
    Sebastian Beyvers, Lukas Jelonek, Alexander Goesmann, Oliver Schwengers.
      The Bakta command line application is widely used and one of the most established tools for bacterial genome annotation. It balances comprehensive annotation with computational efficiency via alignment-free sequence identifications. However, the usage of command line software tools and the interpretation of result files in various formats might be challenging and pose technical barriers. Here, we present the recent updates on the Bakta web server, a user-friendly web interface for conducting and visualizing annotations using Bakta without requiring command line expertise or local computing resources. Key features include interactive visualizations through circular genome plots, linear genome browsers, and searchable data tables facilitating the interpretation of complex annotation results. The web server generates standard bioinformatics outputs (GFF3, GenBank, EMBL) and annotates diverse genomic features, including coding sequences, non-coding RNAs, small open reading frames (sORFs), and many more. The development of an auto-scaling cloud-native architecture and improved database integration led to substantially faster processing times and higher throughputs. The system supports FAIR principles via extensive cross-reference links to external databases, including RefSeq, UniRef, and Gene Ontology. Also, novel features have been implemented to foster sharing and collaborative interpretation of results. The web server is freely available at https://bakta.computational.bio.
    DOI:  https://doi.org/10.1093/nar/gkaf335
  2. Int J Cancer. 2025 Apr 25.
    From non-coding RNAs to cancer regulators: The fascinating world of micropeptides.
    Can Li, Dan Zhang, Jinxi Huang, He Zhou, Tao Song, Xianyao Wang, Qinghong Kong, Liujin Li, Zhaohui Liu, Neng Zhang, Yanxin Lu, Jun Tan, Jidong Zhang.
      Micropeptides are commonly identified as peptides encoded by non-coding RNAs (ncRNAs). In the short open reading frame (sORF) of ncRNAs, there is a base sequence encoding functional micropeptides, which is of great significance in the biological field. Recently, micropeptides regulate diverse processes, including mitochondrial metabolism, calcium transport, mRNA splicing, signal transduction, myocyte fusion, and cellular senescence, regulating the homeostasis of the internal environment and cancer's incidence and progression. Especially, the study of micropeptides in cancer about the potential regulatory mechanism will be conducive to further understanding of the process of cancer initiation and development. More and more research shows micropeptides have been confirmed to play an essential role in the emergence of multiple kinds of cancers, including Breast cancer, Colon cancer, Colorectal cancer, Glioma, Glioblastoma, and Liver cancer. This review presents a comprehensive synthesis of the latest advancements in our understanding of the biological roles of micropeptides in cancer cells, with a particular focus on the regulatory networks involving micropeptides in oncogenesis. The new mode of action of micropeptides provides innovative ideas for cancer diagnosis and treatment. Moreover, we explored the significant capacity of micropeptides as diagnostic biomarkers and targets for anti-cancer therapies in cancer clinical settings, highlighting their role in the development of innovative micropeptide-based diagnostic tools and anti-cancer therapeutics.
    Keywords:  cancer; micropeptides; non‐coding RNAs; sORF
    DOI:  https://doi.org/10.1002/ijc.35459
  3. RNA Biol. 2025 Apr 25.
    The implication of non-AUG-initiated N-terminally extended proteoforms in cancer.
    Rita Pancsa, Dmitry E Andreev, Kellie Dean.
      Dysregulated translation is a hallmark of cancer, and recent genome-wide studies in tumour cells have uncovered widespread translation of non-canonical reading frames that often initiate at non-AUG codons. If an upstream non-canonical start site is located within a frame with an annotated coding sequence (CDS), such translation events can lead to the production of proteoforms with altered N-termini (PANTs). Certain examples of PANTs from oncogenes (e.g. c-MYC) and tumour suppressors (e.g. PTEN) have been previously linked to cancer. We have performed a systematic computational analysis on recently identified non-AUG initiation-derived N-terminal extensions of cancer-associated proteins, and we discuss how these extended proteoforms may acquire new oncogenic properties. We identified loss of stability for the N-terminally extended proteoforms of oncogenes TCF-4 and SOX2. Furthermore, we discovered likely functional short linear motifs within the N-terminal extensions of oncogenes and tumour suppressors (SOX2, SUFU, SFPQ, TOP1 and SPEN/SHARP) that could provide an explanation for previously described functionalities or interactions of the proteins. In all, we identify novel cases where PANTs likely show different localization, functions, partner binding or turnover rates compared to the annotated proteoforms. Therefore, we propose that alterations in the stringency of translation initiation, often seen under conditions of cellular stress, may result in reprogramming of translation to generate novel PANTs that influence cancer progression.
    Keywords:  N-terminal extension; alternative translation start site; non-AUG initiation; proteoforms with altered N-termini; short linear motifs; start codon; translation initiation
    DOI:  https://doi.org/10.1080/15476286.2025.2498203
  4. Front Pharmacol. 2025 ;16 1545575
    Endogenous micropeptides as potential diagnostic biomarkers and therapeutic drugs.
    Aixi Zhong, Shuai Li, Jingxuan Zhang, Jingyuan Zhao, Chenhui Yao.
      Micropeptides, these small proteins derived from non-coding RNA, typically consist of no more than 100 amino acids in length. Despite the challenges in analysis and identification, their various critical functions within organisms cannot be overlooked. They play a significant role in maintaining energy metabolism balance, regulating the immune system, and influencing the development of tumors, which also gives them a decisive impact on the occurrence and development of various diseases. This review aims to outline the role and potential value of micropeptides, introducing their tissue classification and distribution, biological functions, and mechanisms, with a focus on their potential as diagnostic markers and therapeutic drugs.
    Keywords:  diagnostic biomarkers; drugs; micropeptides; noncoding RNAs (ncRNAs); peptide
    DOI:  https://doi.org/10.3389/fphar.2025.1545575
  5. Cell Genom. 2025 Apr 17. pii: S2666-979X(25)00109-0. [Epub ahead of print] 100853
    Morphogenesis, starvation, and light responses in a mushroom-forming fungus revealed by long-read sequencing and extensive expression profiling.
    Botond Hegedüs, Neha Sahu, Balázs Bálint, Sajeet Haridas, Viktória Bense, Zsolt Merényi, Máté Virágh, Hongli Wu, Xiao-Bin Liu, Robert Riley, Anna Lipzen, Maxim Koriabine, Emily Savage, Jie Guo, Kerrie Barry, Vivian Ng, Péter Urbán, Attila Gyenesei, Michael Freitag, Igor V Grigoriev, László G Nagy.
      Mushroom-forming fungi (Agaricomycetes) are emerging as pivotal players in several fields of science and industry. Genomic data for Agaricomycetes are accumulating rapidly; however, this is not paralleled by improvements of gene annotations, which leave gene function notoriously poorly understood. We set out to improve our functional understanding of the model mushroom Coprinopsis cinerea by integrating a new, chromosome-level assembly, high-quality gene predictions, and functional information derived from broad gene-expression profiling data. The new annotation includes 5' and 3' untranslated regions (UTRs), polyadenylation sites (PASs), upstream open reading frames (uORFs), splicing isoforms, and microexons, as well as core gene sets corresponding to carbon starvation, light response, and hyphal differentiation. As a result, the genome of C. cinerea has now become the most comprehensively annotated genome among mushroom-forming fungi, which will contribute to multiple rapidly expanding fields, including research on their life history, light and stress responses, as well as multicellular development.
    Keywords:  Basidiomycota; fruiting body development; fungal genomics; gene function prediction; light response; starvation; transcriptome profiling
    DOI:  https://doi.org/10.1016/j.xgen.2025.100853
  6. Bioinformatics. 2025 Apr 25. pii: btaf250. [Epub ahead of print]
    Popcorn: prediction of short coding and noncoding genomic sequences in prokaryotes.
    Alison Kyrouz, Lian Liu, Lixin Qin, Brian Tjaden.
       SUMMARY: The most challenging prokaryotic genes to identify often correspond to short ORFs (sORFs) encoding small proteins or to noncoding RNAs. RNA-seq experiments commonly evince small transcripts that do not correspond to annotated genes and are candidates for novel coding sORFs or small regulatory RNAs, but it can be difficult to accurately assess whether the numerous small transcripts are coding or not. We present Popcorn (PrOkaryotic Prediction of Coding OR Noncoding), a novel machine learning method for determining whether prokaryotic sequences are coding or noncoding. We find that Popcorn is effective in distinguishing coding from noncoding sequences, including coding sORFs and noncoding RNAs.
    AVAILABILITY AND IMPLEMENTATION: Freely available for use on the web at https://cs.wellesley.edu/∼btjaden/Popcorn. Source code available at https://github.com/btjaden/Popcorn and https://doi.org/10.5281/zenodo.15120075.
    SUPPLEMENTARY INFORMATION: Supplementary material are available at Bioinformatics online.
    DOI:  https://doi.org/10.1093/bioinformatics/btaf250
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