Interaction of Prions Causes Heritable Traits in Saccharomyces cerevisiae

The concept of "protein-based inheritance" defines prions as epigenetic determinants that cause several heritable traits in eukaryotic microorganisms, such as Saccharomyces cerevisiae and Podospora anserina. Previously, we discovered a non-chromosomal factor, [NSI(+)], which possesses the main features of yeast prions, including cytoplasmic infectivity, reversible curability, dominance, and non-Mendelian inheritance in meiosis. This factor causes omnipotent suppression of nonsense mutations in strains of S. cerevisiae bearing a deleted or modified Sup35 N-terminal domain. In this work, we identified protein determinants of [NSI(+)] using an original method of proteomic screening for prions. The suppression of nonsense mutations in [NSI(+)] strains is determined by the interaction between [SWI(+)] and [PIN(+)] prions. Using genetic and biochemical methods, we showed that [SWI(+)] is the key determinant of this nonsense suppression, whereas [PIN(+)] does not cause nonsense suppression by itself but strongly enhances the effect of [SWI(+)]. We demonstrated that interaction of [SWI(+)] and [PIN(+)] causes inactivation of SUP45 gene that leads to nonsense suppression. Our data show that prion interactions may cause heritable traits in Saccharomyces cerevisiae.