bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2022‒11‒06
three papers selected by
Thomas Farid Martínez
University of California, Irvine

  1. Nat Commun. 2022 Oct 31. 13(1): 6515
      Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides but lacking canonical coding sequences. Apparently unable to produce peptides, lncRNA function seems to rely only on RNA expression, sequence and structure. Here, we exhaustively detect in-vivo translation of small open reading frames (small ORFs) within lncRNAs using Ribosomal profiling during Drosophila melanogaster embryogenesis. We show that around 30% of lncRNAs contain small ORFs engaged by ribosomes, leading to regulated translation of 100 to 300 micropeptides. We identify lncRNA features that favour translation, such as cistronicity, Kozak sequences, and conservation. For the latter, we develop a bioinformatics pipeline to detect small ORF homologues, and reveal evidence of natural selection favouring the conservation of micropeptide sequence and function across evolution. Our results expand the repertoire of lncRNA biochemical functions, and suggest that lncRNAs give rise to novel coding genes throughout evolution. Since most lncRNAs contain small ORFs with as yet unknown translation potential, we propose to rename them "long non-canonical RNAs".
  2. J Proteome Res. 2022 Nov 01.
      The 2022 Metrics of the Human Proteome from the HUPO Human Proteome Project (HPP) show that protein expression has now been credibly detected (neXtProt PE1 level) for 18 407 (93.2%) of the 19 750 predicted proteins coded in the human genome, a net gain of 50 since 2021 from data sets generated around the world and reanalyzed by the HPP. Conversely, the number of neXtProt PE2, PE3, and PE4 missing proteins has been reduced by 78 from 1421 to 1343. This represents continuing experimental progress on the human proteome parts list across all the chromosomes, as well as significant reclassifications. Meanwhile, applying proteomics in a vast array of biological and clinical studies continues to yield significant findings and growing integration with other omics platforms. We present highlights from the Chromosome-Centric HPP, Biology and Disease-driven HPP, and HPP Resource Pillars, compare features of mass spectrometry and Olink and Somalogic platforms, note the emergence of translation products from ribosome profiling of small open reading frames, and discuss the launch of the initial HPP Grand Challenge Project, "A Function for Each Protein".
    Keywords:  Biology and Disease-HPP (B/D-HPP); Grand Challenge Project; Human Protein Atlas; Human Proteome Project (HPP); Mass Spectrometry Interactive Virtual Environment (MassIVE); PeptideAtlas; Ribo-Seq; chromosome-centric HPP (C-HPP); missing proteins (MP); neXtProt protein existence (PE metrics); non-MS PE1 proteins; small open reading frames (smORFs); uncharacterized protein existence 1 (uPE1)
  3. Plant Sci. 2022 Oct 31. pii: S0168-9452(22)00344-2. [Epub ahead of print]326 111519
      The plant science community has identified various regulatory components involved in gene expression. With the advancement of approaches and technologies, new layers of gene regulation have been identified, which play essential roles in fine-tuning biological processes. In this area, recently, small peptides emerged as key regulators in gene regulation to control developmental and physiological processes in plants. Various small peptides have also been identified and characterized to elucidate their roles. A class of small peptides, microProteins (miPs), have been shown to contain at least a protein-protein interaction domain with the potential to regulate multi-domain proteins by becoming a part of protein complexes. Recent studies suggest that some pri-miRNAs encode peptides (miPEPs), which are essential components in plant growth and development. This review provides updates about these small peptides, in general, summarizing their potential role in gene regulation and possible mechanism(s) in plants. We also propose that in-depth research on newly identified plant peptides in crops help to provide solutions enabling sustainable agriculture and food production.
    Keywords:  Gene regulation; MicroProteins; Transcription factors; miPEP