bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2020‒08‒23
three papers selected by
Thomas Martinez
Salk Institute for Biological Studies


  1. Exp Cell Res. 2020 Aug 17. pii: S0014-4827(20)30478-X. [Epub ahead of print] 112229
    Renz PF, Francia FV, Sendoel A.
      The 5' untranslated region (5'UTR) is critical in determining post-transcriptional control, which is partly mediated by short upstream open reading frames (uORFs) present in half of mammalian transcripts. uORFs are generally considered to provide functionally important repression of the main-ORF by engaging initiating ribosomes, but under specific environmental conditions such as cellular stress, uORFs can become essential to activate the translation of the main coding sequence. In addition, a growing number of uORF-encoded bioactive microproteins have been described, which have the potential to significantly increase cellular protein diversity. Here we review the diverse cellular contexts in which uORFs play a critical role and discuss the molecular mechanisms underlying their function and regulation. The exciting progress over the last decades in dissecting uORF function suggests that the 5'UTR remains an exciting frontier towards understanding how the cellular proteome is shaped in health and disease.
    Keywords:  5'UTR; Development and Disease; Gene expression regulation; Translational regulation; uORFs
    DOI:  https://doi.org/10.1016/j.yexcr.2020.112229
  2. J Proteome Res. 2020 Aug 19.
    Bartel J, Varadarajan AR, Sura T, Ahrens CH, Maaß S, Becher D.
      Small open reading frame encoded proteins (SEPs) gained increasing interest during the last years due to their broad range of important functions in both, prokaryotes and eukaryotes. In bacteria, signalling, virulence or regulation of enzyme activities have been associated with SEPs. Nonetheless, the number of SEPs detected in large-scale proteome studies is often low as classical methods are biased towards the identification of larger proteins. Here, we present a workflow that allows enhanced identification of small proteins compared to traditional protocols. For this aim, the steps of small protein enrichment, proteolytic digest and database search were reviewed and adjusted to the special requirement of SEPs. Enrichment by the use of small-pore-sized solid-phase material increased the number of identified SEPs by a factor of two and the utilisation of alternative proteases to trypsin reduced spectral counts for larger proteins. The application of the optimised protocol allowed the detection of 210 already annotated proteins up to 100 amino acids length, including 16 proteins below 51 amino acids in the Gram-positive model organism Bacillus subtilis. Moreover, 12% of all identified proteins were up to 100 amino acids which is a significant larger fraction than reported in studies involving traditional proteomics workflows. Finally, the application of an integrated proteogenomics search database and extensive subsequent validation resulted in the confident identification of three novel, not yet annotated SEPs, which are 21, 26 and 42 amino acid long, respectively.
    DOI:  https://doi.org/10.1021/acs.jproteome.0c00286
  3. J Agric Food Chem. 2020 Aug 20.
    Wu LY, Lv Y, Ye Y, Liang YR, Ye JH.
      Accumulation of secondary metabolites in the young shoots of tea plants is developmentally modulated, especially flavonoids. Here, we investigate the developmental regulation mechanism of secondary metabolism in the developing leaves of tea plants using an integrated multi-omic approach. For the pair of Leaf2/Bud, the correlation coefficient of the fold change of mRNA and RPFs abundances involved in flavonoid biosynthesis was 0.9359, being higher than that of RPFs and protein (R2=0.6941). These correlations were higher than the corresponding correlation coefficients for secondary metabolisms and genome-wide scale. Metabolomic analysis demonstrates that the developmental modulations of the structural genes for flavonoid biosynthesis-related pathways align with the concentration changes of catechin and flavonol glycoside groups. Relatively high translational efficiency (TE>2) was observed in the 4 flavonoid structural genes (chalcone isomerase, dihydroflavonol 4-reductase, anthocyanidin synthase and flavonol synthase). In addition, we originally provided the information of identified small open reading frames (small ORFs) and main ORFs in tea leaves, and elaborated the presence of upstream ORFs may have repressive effect on the translation of downstream ORFs. Our data suggest that transcriptional regulation coordinates with translational regulation and may contribute to the elevation of translational efficiencies for the structural genes involved in the flavonoid biosynthesis pathways during tea leaf development.
    DOI:  https://doi.org/10.1021/acs.jafc.0c03341