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

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.