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  • The EMBO Journal (2007) 26, 3794 - 3803
  • doi:10.1038/sj.emboj.7601811

Published online: 2 August 2007

J-protein co-chaperone Sis1 required for generation of [RNQ+] seeds necessary for prion propagation

Rebecca Aron1,2,ab, Takashi Higurashi1,a, Chandan Sahi1 and Elizabeth A Craig1

  1. Department of Biochemistry, University of Wisconsin, Madison, WI, USA
  2. Graduate Program in Biomolecular Chemistry, University of Wisconsin, Madison, WI, USA

Correspondence to:

Elizabeth A Craig, Department of Biochemistry, University of Wisconsin, 441E Biochemistry Addition, 433 Babcock Drive, Madison, WI 53706-1544, USA. Tel.: +1 608 263 7105; Fax: +1 608 262 3453; E-mail: ecraig@wisc.edu

aThese authors contributed equally to this work

bPresent address: Gladstone Institute of Neurological Disease, University of California at San Francisco, San Francisco, CA 94158, USA

Received 22 February 2007; Accepted 2 July 2007

Yeast prions are protein-based genetic elements capable of self-perpetuation. One such prion, [RNQ+], requires the J-protein Sis1, an Ssa Hsp70 co-chaperone, as well as the AAA+ ATPase, Hsp104, for its propagation. We report that, upon depletion of Sis1, as well as upon inactivation of Hsp104, Rnq1 aggregates increased in size. Subsequently, cells having large aggregates, as well as an apparently soluble pool of Rnq1, became predominant in the cell population. Newly synthesized Rnq1 localized to both aggregates and bulk cytosol, suggesting that nascent Rnq1 partitioned into pools of prion and nonprion conformations, and implying that these large aggregates were still active as seeds. Ultimately, soluble Rnq1 predominated, and the prion was lost from the population. Our data suggest a model in which J-protein:Hsp70 machinery functions in prion propagation, in conjunction with Hsp104. Together, these chaperones facilitate fragmentation of prion polymers, generating a sufficient number of seeds to allow efficient conversion of newly synthesized Rnq1 into the prion conformation.

  • Keywords:

    • AAA+ ATPase,
    • Hsp40,
    • Hsp70,
    • Hsp104,
    • [PIN+]