A prion is an infectious protein, a concept developed in studies of scrapie of sheep and of kuru and Creutzfeldt-Jakob disease of humans. An altered form of a protein, on entering a new individual, can convert the normal form into this altered form. This results in loss of the normal form and accumulation of the altered (prion) form, either of which can have physiological effects. I have confirmed that [URE3] requires URE2 for its propagation by a new method using the URE2 gene on a shuttle vector. I have also shown that [URE3] can be cured by growth of cells on rich medium containing 5 mM guanidine HCl, but that the cured cells can again become [URE3]. Finally, overproduction of Ure2p results in a 100-fold increase in the frequency with which cells become [URE3]. These are the properties expected of a yeast prion, not those expected if [URE3] is a DNA or RNA replicon. The [PSI] non-Mendelian element of yeast increases the efficiency of suppression of nonsense and frameshift mutations by classical suppressor tRNAs. [PSI] has similar properties to [URE3], making it likely that [PSI] is also a prion. [PSI] requires the chromosomal gene SUP35 for its propagation. Recessive mutants of SUP35 have the same phenotype as does the presence of [PSI]. [PSI] can be reversibly cured by either 5 mM guanidine HCl or by high osmotic strength. Finally, overproduction of Sup35p results in a 100-fold increase of the conversion of cells from [psi-] to [PSI+]. My proposal that [URE3] and [PSI] are prions of yeast has both provided the first model systems for mammalian prion diseases and supported the notion of prion as protein - only infectious elements.
NIH ExPorter
NIH ExPorter