Abstract
Yeast strains can reversibly interconvert between [PSI+] and [psi-] states. The [PSI+] state is caused by a prion form of the translation termination factor eRF3. The [PSI+] state causes read-through at stop codons and can lead to phenotypic variation, although the molecular mechanisms causing those phenotypic changes remain unknown. We identify an interaction between [PSI+]-induced phenotypic variation and defects in nonstop mRNA decay. Nonstop mRNA decay is triggered when a ribosome reaches the 3' end of the transcript. In contrast, we observed little interaction between [PSI+]-induced phenotypic variation and defects in nonsense-mediated decay, which lead to suppression of premature stop codons. These results suggest that at least some of the phenotypic effects of [PSI+] may be due to read-through of "normal" stop codons, thereby producing extended proteins. Moreover, these observations suggest that nonstop mRNA decay may limit [PSI+]-induced phenotypic variation. Such a process would allow periodic sampling of the 3' UTR, which can diverge rapidly, for novel and beneficial protein extensions.