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Molecular and Cellular Biology, May 2008, p. 3313-3323, Vol. 28, No. 10
0270-7306/08/$08.00+0     doi:10.1128/MCB.01900-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Regulatory Role of the Rnq1 Nonprion 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

Received 20 October 2007/ Returned for modification 26 November 2007/ Accepted 27 February 2008

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, Rnq1100, that deletes the nonprion 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 the Rnq1 prion in the maintenance of heterologous prions and polyQ aggregates. Rnq1 and Rnq1100 form a sodium dodecyl sulfate-stable and Sis1 (an Hsp40 chaperone protein)-containing coaggregate in [PIN⁺] cells. Importantly, Rnq1100 is highly QN-rich and prone to self-aggregate or coaggregate with Rnq1 when coexpressed in [pin^–] cells. However, the [pin^–] Rnq1-Rnq1100 coaggregate does not represent a prion-like aggregate. These findings suggest that [PIN⁺] Rnq1-Rnq1100 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.

Published ahead of print on 10 March 2008.

Supplemental material for this article may be found at http://mcb.asm.org/.