Prions of Yeast and Fungi: Proteins Acting as Genes

Abstract

Just as nucleic acids can carry out enzyme reactions, it has now been found that proteins can be genes. The nonchromosomal genes [URE3], [PSI], [PIN], [SWI], [MCA], [MOT3], and [OCT] of Saccharomyces cerevisiae and [Het-s] of the filamentous fungus Podospora anserina are self-propagating amyloid forms of normal cellular proteins Ure2p, Sup35p, Rnq1p, Swi1p, Mca1p, Mot3p, Cyc8p, and HET-s, respectively. The phenotypes produced are due to the absence of the soluble forms in the [URE3], [PSI], [SWI], and [OCT] cases, but due to the presence of the amyloid forms in [PIN], [MCA], and [Het-s]. The portions of the Ure2p, Sup35p, Rnq1p, Swi1p, Mca1p, and Cyc8p molecules primarily responsible for prion formation and propagation (prion domains) are very rich in asparagine and glutamine residues, unlike the HET-s prion domain or the PrP molecule that plays a central role in the mammalian transmissible spongiform encephalopathies (TSEs). The [Het-s] prion is of particular interest because it apparently carries out a normal function for Podospora, namely, ‘heterokaryon incompatibility’. By contrast, the [URE3] and [PSI+] prions appear to be yeast diseases. Chaperones play a critical role in prion propagation, some by generating seeds for formation of the amyloid filaments and others by blocking prion formation.