bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2025–10–05
two papers selected by
Thomas Farid Martínez, University of California, Irvine
  1. Comprehensive profiling of ribo-seq detected small sequences in yeast reveals robust conservation patterns and their potential mechanisms of origin.
  2. Transcriptome-wide mapping of small ribosomal subunits elucidates scanning mechanisms of translation initiation in the mammalian brain.
  1. BMC Genomics. 2025 Sep 29. 26(1): 856
    Comprehensive profiling of ribo-seq detected small sequences in yeast reveals robust conservation patterns and their potential mechanisms of origin.
    Cristopher Reyes Loaiciga, Weiyi Li, Xin-Qing Zhao, Jing Li.
       BACKGROUND: In the budding yeast Saccharomyces cerevisiae, the widespread adoption of ribosome profiling technology has allowed the discovery of evidence of transcription and translation for thousands of small proteins or microproteins whose importance was once disregarded. Both conserved and evolutionarily short-lived microproteins have demonstrated relevant involvement in biological functions. However, sequences exist in a broad spectrum of conservation. Here, we tested whether these small proteins in yeast detected by ribosome profiling technology have different properties across their levels of conservation, and how do these properties compare with the canonical small protein-coding sequences.
    RESULTS: Here, we applied a phylostratigraphic approach to peptides encoded by small open reading frames. We compared 20,023 ribo-seq-detected small peptides against annotated small proteins belonging to reference annotations on the basis of their respective conservation patterns. We identified 1134 unannotated microproteins that, despite their difficulty in being detected by methods other than ribosome profiling, display hallmarks of functionality such as conservation across many taxonomical levels and signals of purifying selection not dissimilar to those of canonical proteins of comparable length. Sequences that initially did not show evidence of belonging to any gene family were found to possess signals of homology traceable mostly at genus level when compared against noncoding regions and using TBLASTN, but also, to a lesser extent, to species belonging to the phyla Basidiomycota and Microsporidia. In addition, we show an analysis of the mutations behind the origin of small open reading frames exclusive to S. cerevisiae and identified changes in the initiation codon as the most common group of mutations when compared to Saccharomyces paradoxus, the closest species to S. cerevisiae.
    CONCLUSIONS: Our work, by presenting robust analysis of the extended landscape of small proteins in yeast, suggests that small conserved sequences, either canonical or not, possess a shared evolutionary trajectory, as demonstrated by their properties. These results shed some light into the evolutionary processes behind the extended landscape of small proteins in yeast.
    Keywords:   Saccharomyces cerevisiae ; De novo origination; Fungi; Microprotein; Phylostratigraphy; Ribo-seq; Sequence evolution
    DOI:  https://doi.org/10.1186/s12864-025-12064-0
  2. Commun Biol. 2025 Sep 30. 8(1): 1399
    Transcriptome-wide mapping of small ribosomal subunits elucidates scanning mechanisms of translation initiation in the mammalian brain.
    Preeti Madhav Kute, Francois P Pauzin, Kornel Labun, Clive R Bramham, Eivind Valen.
      Neuronal protein synthesis is highly compartmentalised and regulated, with key roles for translation initiation and elongation factors. Ribosome profiling, the most widely used transcriptome-wide method for measuring translation, captures translation elongation, but not the initiation phase involving small ribosomal subunit (SSU) scanning. Here, we adapted ribosome complex profiling (RCP-seq) for mouse dentate gyrus and cerebral cortex, to characterize translation initiation. In both tissues, SSUs accumulate near the start codon on synaptically localised RNAs, and this 'poised' SSU configuration correlates with enhanced translational efficiency. Upstream open reading frames (uORFs) are associated with less poised SSUs, potentially by disassociating the SSUs. We further find that neuron-specific transcripts recruit more ribosomes and are more efficiently translated than glia-specific transcripts. For neuronal transcripts, monosome-preferring mRNAs show less SSU occupancy relative to polysome-preferring mRNAs, suggesting reduced recruitment of ribosomes. In summary, RCP-seq elucidates translation initiation dynamics and cell-type- and transcript-specific regulation in the mammalian brain.
    DOI:  https://doi.org/10.1038/s42003-025-08804-3
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