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 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.