Evolutionary conservation of prion-forming abilities of the yeast Sup35 protein

Saccharomyces cerevisiae prion [PSI] is a self-propagating isoform of the e ukaryotic release factor eRF3 (Sup35p). Sup35p consists of the evolutionary conserved release factor domain (Sup35C) and two evolutionary variable reg ions - Sup35N, which serves as a prion-forming domain in S. cerevisiae, and Sup35M. Here, we demonstrate that the prion form of Sup35p is not observed among industrial and natural strains of yeast. Moreover, the prion ([PSI+] ) state of the endogenous S. cerevisiae Sup35p cannot be transmitted to the next generations via heterologous Sup35p or Sup35NM, originating from the distantly related yeast species Pichia methanolica. This suggests the exist ence of a 'species barrier' in yeast prion conversion. However, the chimeri c Sup35p, containing the Sup35NM region of Pichia, can be turned into a pri on in S. cerevisiae by overproduction of the identical Pichia Sup35NM. Ther efore, the prion-forming potential of Sup35NM is conserved in evolution. In the heterologous system, overproduction of Pichia Sup35p or Sup35NM induce d formation of the prion form of S. cerevisiae Sup35p, albeit less efficien tly than overproduction of the endogenous Sup35p. This implies that prion i nduction by protein overproduction does not require strict correspondence o f the 'inducer' and 'inducee' sequences, and can overcome the 'species barr ier'.