4.5 Article

Translation arrest as a protein quality control system for aberrant translation of the 3′-UTR in mammalian cells

Journal

FEBS LETTERS
Volume 593, Issue 8, Pages 777-787

Publisher

WILEY
DOI: 10.1002/1873-3468.13362

Keywords

3 '-UTR; hydrophobicity; translation arrest

Funding

  1. Japan Society for the Promotion of Science [26116003]
  2. Takeda Science Foundation
  3. Grants-in-Aid for Scientific Research [26116003] Funding Source: KAKEN

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Read-through or mutations of a stop codon resulting in translation of the 3 '-UTR produce potentially toxic C-terminally extended proteins. However, quality control mechanisms for such proteins are poorly understood in mammalian cells. Here, a comprehensive analysis of the 3 '-UTRs of genes associated with hereditary diseases identified novel arrest-inducing sequences in the 3 '-UTRs of 23 genes that can repress the levels of their protein products. In silico analysis revealed that the hydrophobicity of the polypeptides encoded in the 3 '-UTRs is correlated with arrest efficiency. These results provide new insight into quality control mechanisms mediated by 3 '-UTRs to prevent the production of C-terminally extended cytotoxic proteins.

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