Studies of Sup35p : a yeast prion protein

[P S f] is a protein-based heritable phenotype of the yeast Saccharomyces cerevisiae that reflects the prion-like properties of the chromosome-encoded protein Sup35p. This protein is known to be an essential eukaryote polypeptide release factor, namely eRF3.

In a /P S f] strain, the prion conformer of Sup35p exists predominantly as large oligomers, which results in the intracellular depletion of functional release factor (i.e. eRF3) and hence inefficient translation termination. Intriguingly, the prion conformer of Sup35p can be eliminated from [PSI+] strains by growth in the presence of the protein denaturant guanidine hydrochloride (GuHCl). Strains are ‘cured’ of [P S f] by millimolar concentrations of GuFICl, well below that normally required for protein denaturation. It was shown that the kinetics of GuHCl-induced curing fit a segregational model, whereby the heritable [P S f ] determinant is diluted from a culture following the total inhibition of prion replication. A hypothesis for the mechanism of curing is proposed namely that the guanidinium cation inhibits an arginine-modifying enzyme, whose action is required for the post-translational modification of Sup35p and ultimately [P S f] maintenance. The [P S f] determinant does not elicit a disease state in yeast, rather it was shown to confer a selective phenotypic advantage namely enhanced stress tolerance. Moreover, it was demonstrated that the efficiency of translation termination is regulated by environmental stress through a prion-mediated mechanism. This study has addressed the relationship between Sup35p, [PSP] and stress proteins of S.cerevisiae and revealed that prion proteins are not simply pathogenic misshapen proteins and that they may serve as a novel means to regulate many cellular processes in fungi.