bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2022‒07‒17
four papers selected by
Thomas Farid Martínez
University of California, Irvine

  1. Nat Commun. 2022 Jul 09. 13(1): 3984
      TGF-β family proteins including Nodal are known as central regulators of early development in metazoans, yet our understanding of the scope of Nodal signaling's downstream targets and associated physiological mechanisms in specifying developmentally appropriate cell fates is far from complete. Here, we identified a highly conserved, transmembrane micropeptide-NEMEP-as a direct target of Nodal signaling in mesendoderm differentiation of mouse embryonic stem cells (mESCs), and this micropeptide is essential for mesendoderm differentiation. We showed that NEMEP interacts with the glucose transporters GLUT1/GLUT3 and promotes glucose uptake likely through these interactions. Thus, beyond expanding the scope of known Nodal signaling targets in early development and showing that this target micropeptide augments the glucose uptake during mesendoderm differentiation, our study provides a clear example for the direct functional impact of altered glucose metabolism on cell fate determination.
  2. J Proteome Res. 2022 Jul 15.
      Small open reading frame-encoded peptides (SEPs) are microproteins with a length of 100 amino acids or less, which may play a critical role in maintaining cell homeostasis under stress. Therefore, we used mass spectrometry-based proteomics to explore microproteins potentially involved in cellular stress responses in Saccharomyces cerevisiae. A total of 225 microproteins with 1920 unique peptides were identified under six culture conditions: normal, oxidation, starvation, ultraviolet radiation, heat shock, and heat shock with starvation. Among these microproteins, we found 70 SEPs with 75 unique peptides. The annotated microproteins are involved in stress-related processes, such as cell redox reactions, cell wall modification, protein folding and degradation, and DNA damage repair. It suggests that SEPs may also play similar functions under stress conditions. For example, SEP IP_008057, translated from a short coding sequence of YJL159W, may play a role in heat shock. This study identified stress-responsive SEPs in S. cerevisiae and provided valuable information to determine the functions of these proteins, which enrich the genome and proteome of S. cerevisiae and show clues to improving the stress tolerance of S. cerevisiae.
    Keywords:  SEP; heat shock; microprotein; sORF; starvation; ultraviolet irradiation
  3. Genes Dev. 2022 Jun 01. 36(11-12): 647-649
      Polo-like kinase 4 (Plk4) is the master regulator of centriole assembly. Several evolutionarily conserved mechanisms strictly regulate Plk4 abundance and activity to ensure cells maintain a proper number of centrioles. In this issue of Genes & Development, Phan et al. (pp. 718-736) add to this growing list by describing a new mechanism of control that restricts Plk4 translation through competitive ribosome binding at upstream open reading frames (uORFs) in the mature Plk4 mRNA. Fascinatingly, this mechanism is especially critical in the development of primordial germ cells in mice that are transcriptionally hyperactive and thus exquisitely sensitive to Plk4 mRNA regulation.
    Keywords:  Polo-like kinase 4; centriole amplification; primordial germ cell; translational regulation; upstream open reading frame