Dependence and independence of [PSI+] and [PIN+]: a two-prion system in yeast?

• Published in: The EMBO journal Vol. 19; no. 9; pp. 1942 - 1952
• Main Authors: Derkatch, I.L, Bradley, M.E, Masse, S.V.L, Zadorsky, S.P, Polozkov, G.V, Inge-Vechtomov, S.G, Liebman, S.W
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 02.05.2000; Blackwell Publishing Ltd; Oxford University Press
• Subjects: (PIN+) prion; (PSI+) prion; Amino Acid Sequence; Biological Factors - genetics; Biological Factors - physiology; Cold Temperature; Crosses, Genetic; Fungal Proteins - chemistry; Fungal Proteins - genetics; Fungal Proteins - metabolism; Gene Expression; Guanidine - pharmacology; Mitosis; Models, Biological; molecular conformation; Molecular Sequence Data; nonsense suppression; Peptide Fragments - chemistry; Peptide Fragments - genetics; Peptide Fragments - metabolism; Peptide Termination Factors; Phenotype; PIN; Plasmids - genetics; prion; prions; Prions - chemistry; Prions - genetics; Prions - metabolism; Protein Structure, Tertiary - drug effects; proteins; PSI; replication; Saccharomyces cerevisiae; Saccharomyces cerevisiae - chemistry; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae Proteins; Sequence Deletion - genetics; SUP35; Time Factors
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/19.9.1942

The [PSI+] prion can be induced by overproduction of the complete Sup35 protein, but only in strains carrying the non‐Mendelian [PIN+] determinant. Here we demonstrate that just as [psi−] strains can exist as [PIN+] and [pin−] variants, [PSI+] can also exist in the presence or absence of [PIN+]. [PSI+] and [PIN+] tend to be cured together, but can be lost separately. [PSI+]‐related phenotypes are not affected by [PIN+]. Thus, [PIN+] is required for the de novo formation of [PSI+], not for [PSI+] propagation. Although [PSI+] induction is shown to require [PIN+] even when the only overexpressed region of Sup35p is the prion domain, two altered prion domain fragments circumventing the [PIN+] requirement are characterized. Finally, in strains cured of [PIN+], prolonged incubation facilitates the reappearance of [PIN+]. Newly appearing [PIN+] elements are often unstable but become stable in some mitotic progeny. Such reversibility of curing, together with our previous demonstration that the inheritance of [PIN+] is non‐Mendelian, supports the hypothesis that [PIN+] is a prion. Models for [PIN+] action, which explain these findings, are discussed.