Suicidal PSI + is a lethal yeast prion

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.