bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2023‒05‒07
two papers selected by
Thomas Farid Martínez
University of California, Irvine

  1. BMC Genomics. 2023 May 01. 24(1): 226
      Open reading frames (ORFs) with fewer than 100 codons are generally not annotated in genomes, although bona fide genes of that size are known. Newer biochemical studies have suggested that thousands of small protein-coding ORFs (smORFs) may exist in the human genome, but the true number and the biological significance of the micropeptides they encode remain uncertain. Here, we used a comparative genomics approach to identify high-confidence smORFs that are likely protein-coding. We identified 3,326 high-confidence smORFs using constraint within human populations and evolutionary conservation as additional lines of evidence. Next, we validated that, as a group, our high-confidence smORFs are conserved at the amino-acid level rather than merely residing in highly conserved non-coding regions. Finally, we found that high-confidence smORFs are enriched among disease-associated variants from GWAS. Overall, our results highlight that smORF-encoded peptides likely have important functional roles in human disease.
    Keywords:  Comparative genetics; Evolutionary conservation; Human genetic variation; Micropeptides; Small open reading frames
  2. RNA. 2023 May 04. pii: rna.079692.123. [Epub ahead of print]
      Rae1 is a well-conserved endoribonuclease among Gram-positive bacteria, cyanobacteria and the chloroplasts of higher plants. We have previously shown that Rae1 cleaves the Bacillus subtilis yrzI operon mRNA in a translation-dependent manner within a short open reading frame (ORF) called S1025, encoding a 17-amino acid (aa) peptide of unknown function. Here, we map a new Rae1 cleavage site in the bmrBCD operon mRNA encoding a multidrug transporter, within a unannotated 26-aa cryptic ORF that we have named bmrX. Expression of the bmrCD portion of the mRNA is ensured by an antibiotic dependent ribosome attenuation mechanism within the upstream ORF bmrB. Cleavage by Rae1 within bmrX supresses bmrCD expression that escapes attenuation control in the absence of antibiotics. Similar to S1025, Rae1 cleavage within bmrX is both translation- and reading frame-dependent. Consistent with this, we show that translation-dependent cleavage by Rae1 promotes ribosome rescue by the tmRNA.
    Keywords:  <it> Bacillus subtilis </it>; RNA processing and decay; Rae1; translation