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

FEBS Lett. 2019 Apr;593(8):777-787. doi: 10.1002/1873-3468.13362. Epub 2019 Mar 23.

Abstract

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.

Keywords: 3′-UTR; hydrophobicity; translation arrest.

Publication types

  • Editorial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics*
  • HEK293 Cells
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Intracellular Signaling Peptides and Proteins / biosynthesis
  • Intracellular Signaling Peptides and Proteins / chemistry
  • LIM Domain Proteins / biosynthesis
  • LIM Domain Proteins / chemistry
  • Muscle Proteins / biosynthesis
  • Muscle Proteins / chemistry
  • N-Acetylgalactosamine-4-Sulfatase / biosynthesis
  • N-Acetylgalactosamine-4-Sulfatase / chemistry
  • Protein Biosynthesis / genetics*
  • Quality Control

Substances

  • 3' Untranslated Regions
  • FHL1 protein, human
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • Muscle Proteins
  • N-Acetylgalactosamine-4-Sulfatase
  • ARSB protein, human