Multiple Gln/Asn-rich prion domains confer susceptibility to induction of the yeast [PSI(+)] prion.

The yeast prion [PSI(+)] results from self-propagating aggregates of Sup35p. De novo formation of [PSI(+)] requires an additional non-Mendelian trait, thought to result from a prion form of one or more unknown proteins. We find that the Gln/Asn-rich prion domains of two proteins, New1p and Rnq1p, can control susceptibility to [PSI(+)] induction as well as enhance aggregation of a human glutamine expansion disease protein. [PSI(+)] inducibility results from gain-of-function properties of New1p and Rnq1p aggregates rather than from inactivation of the normal proteins. These studies suggest a molecular basis for the epigenetic control of [PSI(+)] inducibility and may reveal a broader role for this phenomenon in the physiology of protein aggregation.