THE PRION MODEL FOR [URE3] OF YEAST - SPONTANEOUS GENERATION AND REQUIREMENTS FOR PROPAGATION

The genetic properties of the non-Mendelian element, [URE3], suggest t hat it is a prion (infectious protein) form of Ure2p, a mediator of ni trogen regulation in Saccharomyces cerevisiae. Into a ure2 Delta strai n (necessarily lacking [URE3]), we introduced a plasmid overproducing Ure2p. This induced the frequent ''spontaneous generation'' of [URE3], with properties identical to the original [URE3], Altering the transl ational frame only in the prion-inducing domain of URE2 shows that it is Ure2 protein (and not URE2 RNA) that induces appearance of [URE3], The proteinase K-resistance of Ure2p is unique to [URE3] strains and i s not seen in nitrogen regulation of normal strains, The prion-inducin g domain of Ure2p (residues 1-65) can propagate [URE3] in the absence of the C-terminal part of the molecule, In contrast, the C-terminal pa rt of Ure2p cannot be converted to the prion (inactive) form without t he prion-inducing domain covalently attached, These experiments suppor t the prion model for [URE3] and extend our understanding of its propa gation.