7 Prions of Yeast and Filamentous Fungi: [URE3], [PSI+], [PIN+], and [Het-s]

Abstract

In 1994, two non-Mendelian genetic elements of Saccharomyces cerevisiae, called [URE3] and [PSI⁺], were discovered to be prion (infectious protein) forms of the chromosomally encoded proteins, Ure2p and Sup35p, respectively (Wickner 1994). [Het-s], a non-Mendelian genetic element of the filamentous fungus Podospora anserina, is a prion of the HET-s protein (Coustou et al. 1997). Recently, [PIN⁺] was found to be a prion form of the yeast Rnq1p (Derkatch et al. 1997, 2001; Sondheimer and Lindquist 2000). Here we describe these phenomena, the evidence that they are prions, and their general implications for prion biology. The yeast system has made possible identification of many cellular factors affecting prion generation, propagation, and curing.

The concept of an infectious protein was first proposed to explain the unusual properties of the agent producing the transmissible spongiform encephalopathies (Griffith 1967). The term “prion” was coined to mean the scrapie agent, including the possibility that it may have no essential nucleic acid component, but was not restricted to this case (Prusiner 1982). We use the term prion here to mean “an infectious protein” (the protein-only model), regardless of the organism or protein, and making no assumptions about the mechanism involved.

One way in which a protein can be a prion is if it has undergone a change such that it no longer carries out its normal function but has acquired the ability to convert the normal form of the protein into the same form as itself, the prion form. By this definition, the prion change need...