Nonsense Mutations in the Yeast Gene Affect the [] Prion Propagation.

The essential gene encodes yeast translation termination factor eRF3. Previously, we isolated nonsense mutations and proposed that the viability of such mutants can be explained by readthrough of the premature stop codon. Such mutations, as well as the prion [], can appear in natural yeast populations, and their combinations may have different effects on the cells. Here, we analyze the effects of the compatibility of mutations with the [] prion in haploid and diploid cells. We demonstrated that mutations are incompatible with the [] prion, leading to lethality of [] haploid cells. In diploid cells the compatibility of [] with depends on how the corresponding diploid was obtained. Nonsense mutations , and are compatible with the [] prion in diploid strains, but affect [] properties and lead to the formation of new prion variant. The only mutation that could replace the wild-type allele in both haploid and diploid [] strains, , led to the prion loss. Possibly, short Sup35 protein, produced from the allele, is included in Sup35 aggregates and destabilize them. Alternatively, single molecules of Sup35 can stick to aggregate ends, and thus interrupt the fibril growth. Thus, we can conclude that mutation prevents [] propagation and can be considered as a new mutation.