SUPPORT FOR THE PRION HYPOTHESIS FOR INHERITANCE OF A PHENOTYPIC TRAIT IN YEAST

A cytoplasmically inherited genetic element in yeast, [PSI+], was conf irmed to be a prionlike aggregate of the cellular protein Sup35 by dif ferential centrifugation analysis and microscopic localization of a Su p35-green fluorescent protein fusion. Aggregation depended on the intr acellular concentration and functional state of the chaperone protein Hsp104 in the same manner as did [PSI+] inheritance. The amino-termina l and carboxyterminal domains of Sup35 contributed to the unusual beha vior of [PSI+]. [PSI+] altered the conformational slate of newly synth esized prion proteins, inducing them to aggregate as well, thus fulfil ling a major tenet of the prion hypothesis.