Degradation of mRNAs that lack a stop codon: a decade of nonstop progress

Abstract

Nonstop decay is the mechanism of identifying and disposing aberrant transcripts that lack in-frame stop codons. It is hypothesized that these transcripts are identified during translation when the ribosome arrives at the 3' end of the mRNA and stalls. Presumably, the ribosome stalling recruits additional cofactors, Ski7 and the exosome complex. The exosome degrades the transcript using either one of its ribonucleolytic activities, and the ribosome and the peptide are both released. Additional precautionary measures by the nonstop decay pathway may include translational repression of the nonstop transcript after translation, and proteolysis of the released peptide by the proteasome. This surveillance mechanism protects the cells from potentially harmful truncated proteins, but it may also be involved in mediating critical cellular functions of transcripts that are prone to stop codon read-through. Important advances have been made in the past decade as we learn that nonstop decay may have implications in human disease.

Figure 1

Pathways for the degradation of normal yeast mRNAs. See text for details.

Figure 2

nonstop mRNAs are rapidly degraded, and may also trigger translational repression and proteolysis. See text for details.