6 Prions of Fungi: [URE3], [PSI], and [Het-s] Discovered as Heritable Traits

Abstract

In 1994, it was proposed that two non-Mendelian genetic elements of Saccharomyces cerevisiae, called [URE3] and [PSI], were in fact prion (infectious protein) forms of the chromosomally encoded proteins, Ure2p and Sup35p, respectively (Wickner 1994). Recently, it has been suggested that [Het-s], a non-Mendelian genetic element of the filamentous fungus Podospora anserina, is a prion of the protein encoded by het-s (Coustou et al. 1997). Here we describe the properties of these phenomena, the evidence that they are prions, and their general implications for prion biology.

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 not restricted to this case (Prusiner 1982). We shall use the term prion here to mean infectious protein (the protein-only model), regardless of the organism or protein, and making no assumptions about the mechanism involved. In general, a prion is a protein that 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 not be one of conformation. A protein methylase might methylate another molecule of itself by mistake and, having done so, the methylated methylase may no longer be able to modify its...