bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2024–06–16
two papers selected by
Thomas Farid Martínez, University of California, Irvine
  1. Beyond traditional translation: ncRNA derived peptides as modulators of tumor behaviors.
  2. Critical cis-parameters influence STructure assisted RNA translation (START) initiation on non-AUG codons in eukaryotes.
  1. J Biomed Sci. 2024 Jun 14. 31(1): 63
    Beyond traditional translation: ncRNA derived peptides as modulators of tumor behaviors.
    Kang Wen, Xin Chen, Jingyao Gu, Zhenyao Chen, Zhaoxia Wang.
      Within the intricate tapestry of molecular research, noncoding RNAs (ncRNAs) were historically overshadowed by a pervasive presumption of their inability to encode proteins or peptides. However, groundbreaking revelations have challenged this notion, unveiling select ncRNAs that surprisingly encode peptides specifically those nearing a succinct 100 amino acids. At the forefront of this epiphany stand lncRNAs and circRNAs, distinctively characterized by their embedded small open reading frames (sORFs). Increasing evidence has revealed different functions and mechanisms of peptides/proteins encoded by ncRNAs in cancer, including promotion or inhibition of cancer cell proliferation, cellular metabolism (glucose metabolism and lipid metabolism), and promotion or concerted metastasis of cancer cells. The discoveries not only accentuate the depth of ncRNA functionality but also open novel avenues for oncological research and therapeutic innovations. The main difficulties in the study of these ncRNA-derived peptides hinge crucially on precise peptide detection and sORFs identification. Here, we illuminate cutting-edge methodologies, essential instrumentation, and dedicated databases tailored for unearthing sORFs and peptides. In addition, we also conclude the potential of clinical applications in cancer therapy.
    Keywords:  Cancer; Peptides; Protein; circRNAs; lncRNAs; ncRNA
    DOI:  https://doi.org/10.1186/s12929-024-01047-0
  2. NAR Genom Bioinform. 2024 Jun;6(2): lqae065
    Critical cis-parameters influence STructure assisted RNA translation (START) initiation on non-AUG codons in eukaryotes.
    Antonin Tidu, Fatima Alghoul, Laurence Despons, Gilbert Eriani, Franck Martin.
      In eukaryotes, translation initiation is a highly regulated process, which combines cis-regulatory sequences located on the messenger RNA along with trans-acting factors like eukaryotic initiation factors (eIF). One critical step of translation initiation is the start codon recognition by the scanning 43S particle, which leads to ribosome assembly and protein synthesis. In this study, we investigated the involvement of secondary structures downstream the initiation codon in the so-called START (STructure-Assisted RNA translation) mechanism on AUG and non-AUG translation initiation. The results demonstrate that downstream secondary structures can efficiently promote non-AUG translation initiation if they are sufficiently stable to stall a scanning 43S particle and if they are located at an optimal distance from non-AUG codons to stabilize the codon-anticodon base pairing in the P site. The required stability of the downstream structure for efficient translation initiation varies in distinct cell types. We extended this study to genome-wide analysis of functionally characterized alternative translation initiation sites in Homo sapiens. This analysis revealed that about 25% of these sites have an optimally located downstream secondary structure of adequate stability which could elicit START, regardless of the start codon. We validated the impact of these structures on translation initiation for several selected uORFs.
    DOI:  https://doi.org/10.1093/nargab/lqae065
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