A regulatory role of the Rnq1 nonprion domain for prion propagation and polyglutamine aggregates

Prions are infectious, self-propagating protein conformations. Rnq1 is required for the yeast Saccharomyces cerevisiae prion [PIN⁺], which is necessary for the de novo induction of a second prion, [PSI⁺]. Here we isolated a [PSI⁺]-eliminating mutant, Rnq1Δ100, that deletes the nonprion domain of Rnq1. Rnq1Δ100 inhibits not only [PSI ⁺] prion propagation but also [URE3] prion and huntingtin's polyglutamine aggregate propagation in a [PIN⁺] background but not in a [pin^-] background. Rnq1Δ100, however, does not eliminate [PIN⁺]. These findings are interpreted as showing a possible involvement of the Rnq1 prion in the maintenance of heterologous prions and polyQ aggregates. Rnq1 and Rnq1Δ100 form a sodium dodecyl sulfate-stable and Sis1 (an Hsp40 chaperone protein)-containing coaggregate in [PIN ⁺] cells. Importantly, Rnq1Δ100 is highly QN-rich and prone to self-aggregate or coaggregate with Rnq1 when coexpressed in [pin^-] cells. However, the [pin^-] Rnq1-Rnq1Δ100 coaggregate does not represent a prion-like aggregate. These findings suggest that [PIN⁺] Rnq1-Rnq1Δ100 aggregates interact with other transmissible and nontransmissible amyloids to destabilize them and that the nonprion domain of Rnq1 plays a crucial role in self-regulation of the highly reactive QN-rich prion domain of Rnq1.