The PNM2 mutation in the prion protein domain of SUP35 has distinct effects on different variants of the [PSI⁺] prion in yeast

We have previously described different variants of the yeast prion [PSI⁺] that can be obtained and maintained in the same genetic background. These [PSI⁺] variants, which differ in the efficiency of nonsense suppression, mitotic stability and the efficiency of curing by GuHCl, may correspond to different [PSI⁺] prion conformations of Sup35p or to different types of prion aggregates. Here we investigate the effects of overexpressing a mutant allele of SUP35 and find different effects on weak and strong [PSI⁺] variants: the suppressor phenotype of weak [PSI⁺] factors is increased, whereas the suppressor effect of strong [PSI⁺] factors is reduced. The SUP35 mutation used was originally described as a 'Psi no more' mutation (PNM2) because it caused loss of [PSI⁺]. However, none of the [PSI⁺] variants in the strains used in our study were cured by PNM2. Indeed, when overexpressed, PNM2 induced the de novo appearance of both weak and strong [PSI⁺] variants with approximately the same efficiency as the overexpressed wild-type SUP35 allele. Our data suggest that the change in the region of oligopeptide repeats in the Sup35p N-terminus due to the PNM2 mutation modifies, but does not impair, the function of the prion domain of Sup35p.