bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2022–06–26
three papers selected by
Thomas Farid Martínez, University of California, Irvine



  1. Cell Rep. 2022 Jun 21. pii: S2211-1247(22)00770-7. [Epub ahead of print]39(12): 110984
    Global Phage Small Open Reading Frame (GP-SmORF) Consortium
      Small genes (<150 nucleotides) have been systematically overlooked in phage genomes. We employ a large-scale comparative genomics approach to predict >40,000 small-gene families in ∼2.3 million phage genome contigs. We find that small genes in phage genomes are approximately 3-fold more prevalent than in host prokaryotic genomes. Our approach enriches for small genes that are translated in microbiomes, suggesting the small genes identified are coding. More than 9,000 families encode potentially secreted or transmembrane proteins, more than 5,000 families encode predicted anti-CRISPR proteins, and more than 500 families encode predicted antimicrobial proteins. By combining homology and genomic-neighborhood analyses, we reveal substantial novelty and diversity within phage biology, including small phage genes found in multiple host phyla, small genes encoding proteins that play essential roles in host infection, and small genes that share genomic neighborhoods and whose encoded proteins may share related functions.
    Keywords:  CP: Microbiology; MetaRibo-Seq; comparative genomics; gene families; microbiome; phage; sORFs; small genes
    DOI:  https://doi.org/10.1016/j.celrep.2022.110984
  2. Yi Chuan. 2022 Jun 20. 44(6): 478-490
      With the rapid development of computational biology and deep sequencing technology, more and more studies have shown that a large number of non-classical open reading frames that have not been annotated and hidden in non-coding RNA can encode functional micropeptide. This article reviewed the current research status and technology strategy of gene sources, biological properties, predicted methods and functional verification of micropeptide, providing theoretical and reference basis for the subsequent discovery of micropeptides, research on regulatory mechanisms and development of novel targets and biomarkers.
    Keywords:  functional micropeptides; noncoding RNA; sORFs
    DOI:  https://doi.org/10.16288/j.yczz.22-007
  3. Front Cell Dev Biol. 2022 ;10 901351
      Recent studies have shown that hundreds of small proteins were occulted when protein-coding genes were annotated. These proteins, called alternative proteins, have failed to be annotated notably due to the short length of their open reading frame (less than 100 codons) or the enforced rule establishing that messenger RNAs (mRNAs) are monocistronic. Several alternative proteins were shown to be biologically active molecules and seem to be involved in a wide range of biological functions. However, genome-wide exploration of the alternative proteome is still limited to a few species. In the present article, we describe a deep peptidomics workflow which enabled the identification of 401 alternative proteins in Drosophila melanogaster. Subcellular localization, protein domains, and short linear motifs were predicted for 235 of the alternative proteins identified and point toward specific functions of these small proteins. Several alternative proteins had approximated abundances higher than their canonical counterparts, suggesting that these alternative proteins are actually the main products of their corresponding genes. Finally, we observed 14 alternative proteins with developmentally regulated expression patterns and 10 induced upon the heat-shock treatment of embryos, demonstrating stage or stress-specific production of alternative proteins.
    Keywords:  alternative proteins; mass spectrometry; microprotein; peptidomics; short open reading frame–encoded polypeptide
    DOI:  https://doi.org/10.3389/fcell.2022.901351