bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2026–02–22
five papers selected by
Thomas Farid Martínez, University of California, Irvine



  1. Bioinform Adv. 2026 ;6(1): vbag031
       Motivation: The advent of ribosome profiling (an adaptation of RNA sequencing) to determine the translatome, has led to a huge improvement in our understanding of what parts of the transcriptome are translated. Many alternative open reading frames (ORFs) are now regularly being detected such as out-of-frame, overlapping, upstream or downstream reading frames, and alternative reading frames using non-canonical start codons. Various tools have been developed for the detection of such novel ORFs, but they lack the capacity to visually inspect reads-an important aspect of validation and prediction of translation.
    Results: The integrated and visualisation of ribosome profiling and RNA sequencing reads enables discrimination between transcriptional and translational signals, facilitating validation of predicted novel open reading frames. Furthermore, the inclusion of complementary evidence such as proteomic and long-read sequencing enables further validation of predicted novel open reading frames.
    Availability and implementation: Here, we present, InspectorORF (https://www.github.com/aylz83/inspectorORF), an R package that readily plots ribosome profiling reads, alongside RNA sequencing reads across transcripts and/or ORFs. Additionally, custom information can be plotted including data from additional conditions and samples, proteomic analyses and reads from long-read sequencing.
    DOI:  https://doi.org/10.1093/bioadv/vbag031
  2. Plant Physiol. 2026 Feb 06. pii: kiag047. [Epub ahead of print]200(2):
      Unraveling the complexities of genomic data has revealed that the protein coding capacity of eukaryotic genomes has been underestimated. Eukaryotic genomes contain numerous unannotated short open reading frames (sORFs) that, localized in different types of RNA molecules, including long non-coding RNAs, may encode and produce biologically functional peptides. This study focuses on the characterization of the Arabidopsis (Arabidopsis thaliana) sORF-derived flower peptidome, using the floral homeotic mutants apetala1, apetala2, apetala3, pistillata, and agamous in comparison to the wild type. For peptide identification by mass spectrometry (MS), we created an extensive database of hypothetical Arabidopsis peptides, which comprised putative sORF-encoded peptides from intergenic regions, untranslated regions, "non-coding" RNAs and other transcripts. In total, 1,874 hypothetical peptides were detected by MS, of which 132 were selected as higher-confidence peptides for further studies. Sixty of these higher-confidence peptides were predicted to be specifically expressed, or at least enriched, in particular floral organs. Approximately 25% of them belonged to putative gene families in A. thaliana, and 103 had potential homologs in other plant species. Additionally, distinct gene expression patterns were observed, in many cases consisting of specific expression in stamens during flower development.
    DOI:  https://doi.org/10.1093/plphys/kiag047
  3. Adv Sci (Weinh). 2026 Feb 20. e23401
      Few studies have explored the functions of peptides encoded by open reading frames (ORFs) in annotated noncoding regions, particularly the 3' untranslated regions (3' UTRs). Although translated ORFs in 5' UTRs (5' ORFs) have been shown to inhibit translation of their corresponding main ORFs (mORFs), the roles of 3' ORFs remain poorly understood. This study analyzes translational regulation across ten developmental stages of maize (Zea mays) anthers and finds that peptides translated from 5' or 3' ORFs can represent misidentified isoforms, with 3' ORFs potentially linked to anther sterility. Notably, the cloned APV1 locus, whose mutation causes male sterility, exemplifies this relationship. Genome-wide translation profiles further reveal enrichment of photosynthesis-related genes during Phase III (the binucleate microspore stage). The presence of stomata and the observed low electron transport rate and net photosynthetic rate suggest that anthers assimilate CO2 with limited photosynthetic efficiency via a pathway distinct from typical C4 photosynthesis. Overall, this study identifies 3' ORFs as potential targets for generating male-sterile maize lines and provides new insights into anther photosynthetic activity.
    Keywords:  3′ untranslated region; anther; anther development; maize; photosynthesis; translational regulation
    DOI:  https://doi.org/10.1002/advs.202523401
  4. Neoplasia. 2026 Feb 14. pii: S1476-5586(26)00016-3. [Epub ahead of print]73 101287
       BACKGROUND: Metabolic reprogramming is a hallmark of colorectal cancer (CRC), yet the molecular regulators that orchestrate this process remain incompletely understood. Although many long non-coding RNAs (lncRNAs) possess protein-coding potential, their translational products and metabolic functions have been largely overlooked. Here, we identify MUCP1, a microprotein encoded by the lncRNA MUC20-OT1, as a critical regulator of mitochondrial metabolism and epigenetic remodeling in CRC.
    METHODS: Multi-omics data were integrated to identify MUC20-OT1 as a candidate lncRNA encoding a functional microprotein. Fusion reporter plasmids, mass spectrometry, and immunoblotting were used to validate MUCP1 translation and mitochondrial localization. Functional assays, metabolomic profiling, 13C5-glutamine isotope tracing, subcellular succinate quantification, CUT&Tag, and xenograft models were performed to investigate the role of MUCP1 in facilitating mitochondrial succinate export and maintaining glutamine metabolism homeostasis.
    RESULTS: The microprotein MUCP1, encoded by the lncRNA MUC20-OT1, serves as an auxiliary regulator of SLC25A10-mediated mitochondrial succinate transport. MUCP1 is upregulated during CRC progression and localizes in the mitochondrial outer membrane, where it facilitates the balance of mitochondrial succinate metabolism. Elevated extramitochondrial succinate subsequently enhances H3K4me3 histone modifications, promoting the transcription of enzymes involved in glutamine metabolism and sustaining the high metabolic demands of CRC cells.
    CONCLUSIONS: This study identifies MUCP1 as a novel lncRNA-encoded microprotein that maintains metabolic homeostasis in CRC by coupling mitochondrial succinate transport to histone methylation. MUCP1 might be a promising metabolic vulnerability and therapeutic target in CRC.
    Keywords:  Glutamine metabolism; H3K4me3; MUCP1; SLC25A10; Succinate
    DOI:  https://doi.org/10.1016/j.neo.2026.101287
  5. Bioinformatics. 2026 Feb 17. pii: btag082. [Epub ahead of print]
       SUMMARY: Accurate annotation of coding sequences and translational features within transcript models is essential for interpreting assembled transcriptomes and their functional potential. Existing open reading frame (ORF) prediction tools typically operate on transcript FASTA files and do not reintegrate coding sequence (CDS) information back into transcript models, limiting their utility in long-read sequencing workflows where GTF/GFF annotations are the primary output. We present ORFannotate, a lightweight, GTF-native Python command-line tool that predicts ORFs from transcript annotations and reinserts precise, exon-aware CDS and UTR features into the original GTF/GFF file. In addition, ORFannotate provides biologically informative translational context by annotating Kozak sequence strength, detecting non-overlapping upstream ORFs (uORFs) with coding probabilities, characterising 5' and 3' untranslated regions (UTRs), and predicting nonsense-mediated decay (NMD) susceptibility. All annotations are consolidated in a transcript-level summary to support downstream analysis. By generating GTF files with accurate CDS annotations, ORFannotate facilitates reproducible analysis of both long- and short-read transcriptomes and integrates seamlessly with visualization tools, genome browsers, and comparative transcript analysis workflows. ORFannotate is fast, scalable and provides a practical solution for transcriptome annotation beyond coding potential prediction alone.
    AVAILABILITY AND IMPLEMENTATION: ORFannotate is implemented in Python and freely available under the GNU General Public License v3 (GPL-3.0) at: https://github.com/egustavsson/ORFannotate (DOI: https://doi.org/10.5281/zenodo.16812866).
    SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
    DOI:  https://doi.org/10.1093/bioinformatics/btag082