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

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 nora 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.