A Regulatory Role of the Rnq1 Non-Prion Domain for Prion Propagation and Polyglutamine Aggregates

Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan

^* To whom correspondence should be addressed. Email: nak{at}ims.u-tokyo.ac.jp.

	Abstract

Prions are infectious, self-propagating protein conformations. Rnq1 is required for the yeast prion [PIN⁺], which is necessary for the de novo induction of a second prion, [PSI⁺]. Here we isolate a [PSI⁺]-eliminating mutant, Rnq1100, that deletes the non-prion domain of Rnq1. Rnq1100 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. Rnq1100, however, does not eliminate [PIN⁺]. These findings are interpreted as showing a possible involvement of Rnq1 prion in the maintenance of heterologous prions and polyQ aggregates. Rnq1 and Rnq1100 form a SDS-stable and Sis1 (a Hsp40 chaperone protein)-containing co-aggregate in [PIN⁺] cells. Importantly, Rnq1100 is highly QN-rich and prone to self-aggregate or co-aggregate with Rnq1 when co-expressed in [pin^-] cells. However, the [pin^-] Rnq1-Rnq1100 co-aggregate does not represent a prion-like aggregate. These findings suggest that [PIN⁺] Rnq1-Rnq1100 aggregates interact with other transmissible and non-transmissible amyloids to destabilize them, and that the non-prion domain of Rnq1 plays a crucial role to self-regulate the highly reactive QN-rich prion domain of Rnq1.