A Regulatory Role of the Rnq1 Nonprion Domain for Prion Propagation and Polyglutamine Aggregates
ABSTRACT 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.