biostudies-literatureUnknown108(13)McGlinchey RPIntramural NIH HHS[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 Proceedings of the National Academy of Sciences of the United States of America5337-41https://www.ebi.ac.uk/biostudies/studies/S-EPMC3069153biostudies-literatureSuicidal [PSI+] is a lethal yeast prion.PMC3069153Wickner RBKryndushkin DMcGlinchey RPfalseSuicidal [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 2011-01-01T00:00:00Z2011 Mar2025-04-21T21:17:19.815Z2019-03-27T00:40:17ZS-EPMC30691532140294710.1073/pnas.1102762108