Suicidal [ PSI + ] is a lethal yeast prion

Abstract

[PSI⁺] is a prion of the essential translation termination factor Sup35p. Although mammalian prion infections are uniformly fatal, commonly studied [PSI⁺] variants do not impair growth, leading to suggestions that [PSI⁺] may protect against stress conditions. We report here that over half of [PSI⁺] variants are sick or lethal. These “killer [PSI⁺]s” are compatible with cell growth only when also expressing minimal Sup35C, lacking the N-terminal prion domain. The severe detriment of killer [PSI⁺] results in rapid selection of nonkiller [PSI⁺] variants or loss of the prion. We also report variants of [URE3], a prion of the nitrogen regulation protein Ure2p, that grow much slower than ure2Δ cells. Our findings give a more realistic picture of the impact of the prion change than does focus on “mild” prion variants.