Prions of Yeast From Cytoplasmic Genes to Heritable Amyloidosis

It was believed that only proteins could carry out enzymatic reactions, and only nucleic acids could mediate inheritance. In recent years, the work of Cech and Altman and others has shown that nucleic acids can catalyze reactions. Now it has been shown that, in yeast, proteins can mediate inheritance. The infectious protein (prion) concept arose from studies of the transmissible spongiform encephalopathies (TSEs) of mammals (1 ), and several lines of evidence suggest that TSEs are indeed caused by infectious forms of the PrP protein, but the absence of definitive proof has left substantial doubt and disagreement on this point (2 –6 ). The ease of genetic manipulation of yeast offers experimental possibilities not yet available even in the mouse system. This enabled the discovery of yeast prions (7 ), and has facilitated the rapid characterization of these systems. The parallels between the yeast and mammalian systems are striking. Moreover, because both of the yeast prion systems appear to involve self-propagating amyloid forms of the respective proteins, these systems may also serve as models for the broader class of diseases for which amyloid accumulation is a central feature. The discovery of the [HET-s] prion of the filamentous fungus Podospora , another genetically manipulable system, adds a new dimension to prion studies (8 ).