MCB Accepts, published online ahead of print on 10 March 2008

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kurahashi, H. Articles by Nakamura, Y. Search for Related Content PubMed PubMed Citation Articles by Kurahashi, H. Articles by Nakamura, Y.

 Previous Article  |  Next Article 

Mol. Cell. Biol. doi:10.1128/MCB.01900-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

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

Hiroshi Kurahashi, Masao Ishiwata, Shoichiro Shibata, and Yoshikazu Nakamura^*

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.

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.

This article has been cited by other articles:

• Kurahashi, H., Shibata, S., Ishiwata, M., Nakamura, Y. (2009). Selfish prion of Rnq1 mutant in yeast. GENES CELLS 14: 659-668 [Abstract] [Full Text]  
• Summers, D. W., Douglas, P. M., Ren, H.-Y., Cyr, D. M. (2009). The Type I Hsp40 Ydj1 Utilizes a Farnesyl Moiety and Zinc Finger-like Region to Suppress Prion Toxicity. J. Biol. Chem. 284: 3628-3639 [Abstract] [Full Text]  
• Ishiwata, M., Kurahashi, H., Nakamura, Y. (2009). A G-protein {gamma} subunit mimic is a general antagonist of prion propagation in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 106: 791-796 [Abstract] [Full Text]