bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2021‒05‒23
two papers selected by
Thomas Martinez
Salk Institute for Biological Studies

  1. BMC Mol Cell Biol. 2021 May 16. 22(1): 29
      BACKGROUND: A large fraction of genes contains upstream ORFs (uORFs) in the 5' untranslated region (5'UTR). The translation of uORFs can inhibit the translation of the main coding sequence, for example by causing premature dissociation of the two ribosomal units or ribosome stalling. However, it is currently unknown if most uORFs are inhibitory or if this activity is restricted to specific cases. Here we interrogate ribosome profiling data from three different stress experiments in yeast to gain novel insights into this question.RESULTS: By comparing ribosome occupancies in different conditions and experiments we obtain strong evidence that, in comparison to primary coding sequences (CDS), which undergo translational arrest during stress, the translation of uORFs is mostly unaffected by changes in the environment. As a result, the relative abundance of uORF-encoded peptides increases during stress. In general, the changes in the translational efficiency of regions containing uORFs do not seem to affect downstream translation. The exception are uORFs found in a subset of genes that are significantly up-regulated at the level of translation during stress; these uORFs tend to be translated at lower levels in stress conditions than in optimal growth conditions, facilitating the translation of the CDS during stress. We find new examples of uORF-mediated regulation of translation, including the Gcn4 functional homologue fil1 and ubi4 genes in S. pombe.
    CONCLUSION: We find evidence that the relative amount of uORF-encoded peptides increases during stress. The increased translation of uORFs is however uncoupled from the general CDS translational repression observed during stress. In a subset of genes that encode proteins that need to be rapidly synthesized upon stress uORFs act as translational switches.
  2. Biochemistry (Mosc). 2021 05;86(5): 551-562
      It was recently found that the primary transcripts of some microRNA genes (pri-miRNAs) are able to express peptides with 12 to 40 residues in length. These peptides, called miPEPs, participate in the transcriptional regulation of their own pri-miRNAs. In our previous studies, we used bioinformatic approach for comparative analysis of pri-miRNA sequences in plant genomes to identify a new group of miPEPs (miPEP-156a peptides) encoded by pri-miR156a in several dozen species of the Brassicaceae family. Exogenous miPEP-156a peptides could efficiently penetrate into the plant seedlings through the root system and spread systemically to the leaves. The peptides produced moderate morphological effect accelerating primary root growth. In parallel, the miPEP-156a peptides upregulated expression of their own pri-miR156a. Importantly, the observed effects at both morphological and molecular levels correlated with the peptide ability to quickly translocate into the cell nucleus and to bind chromatin. In this work, we established secondary structure of the miPEP-156a and demonstrated its changes induced by formation of the peptide complex with DNA.
    Keywords:  DNA-binding peptides; microRNA; microRNA primary transcripts; protein import into the nucleus; short open reading frame; transcription regulation; translation of microRNA primary transcripts