Genetic interactions between [PSI~+] and nonstop mRNA decay affect phenotypic variation

摘要

Yeast strains can reversibly interconvert between [PSI~+] and [psi~-] states. The [PSI~+] state is caused by a prion form of the translation terminatior. 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.