GENESIS AND VARIABILITY OF [PSI] PRION FACTORS IN SACCHAROMYCES-CEREVISIAE

We have previously shown that multicopy plasmids containing the comple te SUP35 gene are able to induce the appearance of the non-Mendelian f actor [PSI]. This result was later interpreted by others as a crucial piece of evidence for a model postulating that [PSI] is a self-modifie d, prion-like conformational derivative of the Sup35 protein. Here we support this interpretation by proving that it is the overproduction o f Sup35 protein, and not the excess of SUP35 DNA Or mRNA that causes t he appearance of [PSI]. We also show that the ''prion-inducing domain' ' of Sup35p is in the N-terminal region, which, like the ''prion-induc ing domain'' of another yeast prion, Ure2p, was previously shown to be distinct from the functional domain of the protein. This suggests tha t such a chimeric organization may be a common pattern of some prion e lements. Finally, we find that [PSI] factors of different efficiencies and different mitotic stabilities are induced in the same yeast strai n by overproduction of the identical Sup35 protein. We suggest that th e different [PSI]-containing derivatives are analogous to the mysterio us mammalian prion strains and result from different conformational va riants of Sup35p.