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

Satoshi Hashimoto1, Risa Nobuta1, Toshiaki Izawa1

  • 1Graduate School of Pharmaceutical Science, Tohoku University, Sendai, Japan.

FEBS Letters
|March 19, 2019
PubMed

Insights

Novel sequences in 3' untranslated regions (3'-UTRs) can stop the production of toxic, extended proteins in mammalian cells. This discovery enhances understanding of cellular quality control for preventing harmful protein synthesis.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Translation of 3 acronym{'}untranslated regions (3 acronym{'}UTRs) due to read-through or stop codon mutations can generate toxic, C-terminally extended proteins.
  • Cellular quality control mechanisms for these aberrant proteins in mammalian cells are not well understood.

Discussion:

  • A comprehensive analysis of 3 acronym{'}UTRs from hereditary disease genes identified novel arrest-inducing sequences.
  • These sequences effectively repress the protein product levels of their respective genes.
  • In silico analysis indicated a correlation between polypeptide hydrophobicity encoded in the 3 acronym{'}UTR and the efficiency of translation arrest.

Key Insights:

  • Discovery of novel 3 acronym{'}UTR-mediated arrest sequences that regulate protein levels.
  • Identification of a link between polypeptide hydrophobicity and translation arrest efficiency.
  • New insights into cellular quality control pathways preventing cytotoxic protein production.

Outlook:

  • Further characterization of these 3 acronym{'}UTR elements could reveal new therapeutic targets for genetic diseases.
  • Understanding these mechanisms may inform strategies for controlling protein expression.
  • Potential applications in synthetic biology for regulating gene expression.

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