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Vol. 17, Issue 3, 1176-1183, March 2006

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Cip1 and Cip2 Are Novel RNA-Recognition-Motif Proteins That Counteract Csx1 Function during Oxidative Stress

Victoria Martín ^*, Miguel A. Rodríguez-Gabriel ^* , W. Hayes McDonald , Stephen Watt , John R. Yates, III , Jürg Bähler , and Paul Russell ^* 

^* Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037; Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037; and The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom

Submitted September 9, 2005; Revised December 13, 2005; Accepted January 3, 2006
Monitoring Editor: Mark Solomon

Eukaryotic cells reprogram their global patterns of gene expression in response to stress. Recent studies in Schizosaccharomyces pombe showed that the RNA-binding protein Csx1 plays a central role in controlling gene expression during oxidative stress. It does so by stabilizing atf1⁺ mRNA, which encodes a subunit of a bZIP transcription factor required for gene expression during oxidative stress. Here, we describe two related proteins, Cip1 and Cip2, that were identified by multidimensional protein identification technology (MudPIT) as proteins that coprecipitate with Csx1. Cip1 and Cip2 are cytoplasmic proteins that have RNA recognition motifs (RRMs). Neither protein is essential for viability, but a cip1 cip2 strain grows poorly and has altered cellular morphology. Genetic epistasis studies and whole genome expression profiling show that Cip1 and Cip2 exert posttranscriptional control of gene expression in a manner that is counteracted by Csx1. Notably, the sensitivity of csx1 cells to oxidative stress and their inability to induce expression of Atf1-dependent genes are partially rescued by cip1 and cip2 mutations. This study emphasizes the importance of a modulated mRNA stability in the eukaryotic stress response pathways and adds new information to the role of RNA-binding proteins in the oxidative stress response.

Present address: Departamento de Microbiologia II, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.

Address correspondence to: Paul Russell (prussell{at}scripps.edu).

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