Multiple GIn/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, tho ught to result from a prion form of one or more unknown proteins. We find t hat the Gln/Asn-rich prion domains of two proteins, New1p and Rnq1p, can co ntrol susceptibility to [PSI+] induction as well as enhance aggregation of a human glutamine expansion disease protein. [PSI+] inducibility results fr om gain-of-function properties of New1p and Rnq1p aggregates rather than fr om inactivation of the normal proteins. These studies suggest a molecular b asis for the epigenetic control of [PSI+] inducibility and may reveal a bro ader role for this phenomenon in the physiology of protein aggregation.