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

摘要

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.