MCB Accepts, published online ahead of print on 12 October 2009

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Mol. Cell. Biol. doi:10.1128/MCB.00842-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Cwc23, an essential J-protein critical for pre-mRNA splicing with a dispensable J-domain

Chandan Sahi, Thomas Lee, Maki Inada, Jeffrey A. Pleiss, and Elizabeth A. Craig^*

Department of Biochemistry, 433 Babcock Drive, University of Wisconsin – Madison, Madison WI 53706; Department of Molecular Biology and Genetics, 451 Biotechnology Building, Cornell University, Ithaca NY 14853

^* To whom correspondence should be addressed. Email: ecraig{at}wisc.edu.

J-proteins are structurally diverse, obligatory co-chaperones of Hsp70s, each with a highly conserved J-domain that plays a critical role in stimulation of Hsp70's ATPase activity. The essential protein, Cwc23, is one of 13 J-proteins found in the cytosol and/or nucleus of Saccharomyces cerevisiae. We report that a partial loss-of-function CWC23 mutant has severe, global defects in pre-mRNA splicing. This mutation leads to accumulation of the excised, lariat form of the intron, as well as unspliced pre-mRNA, suggesting a role for Cwc23 in spliceosome disassembly. Such a role is further supported by the observation that this mutation results in reduced interaction between Cwc23 and Ntr1 (SPP382), a known component of the disassembly pathway. However, Cwc23 is a very atypical J-protein. Its J-domain, although functional, is dispensable for both cell viability and pre-mRNA splicing. Nevertheless, strong genetic interactions were uncovered between point mutations encoding alterations in Cwc23's J-domain and either Ntr1 or Prp43, a DExD/H-box helicase essential for spliceosome disassembly. These genetic interactions suggest that Hsp70-based chaperone machinery does play a role in the disassembly process. Cwc23 provides a unique example of a J-protein; its partnership with Hsp70 plays an auxiliary, rather than a central, role in its essential cellular function.