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MBC in Press, published online ahead of print January 11, 2006
Mol. Biol. Cell 10.1091/mbc.E05-09-0847

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Submitted on September 9, 2005
Revised on December 13, 2005
Accepted on January 3, 2006

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

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

Departments of *Molecular Biology and {ddagger}Cell Biology, The Scripps Research Institute, La Jolla, CA 92037; {sect}The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom

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 multi-dimensional 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{Delta} cip2{Delta} strain grows poorly and has altered cellular morphology. Genetic epistasis studies and whole genome expression profiling show that Cip1 and Cip2 exert post-transcriptional control of gene expression in a manner that is counteracted by Csx1. Notably, the sensitivity of csx1{Delta} cells to oxidative stress and their inability to induce expression of Atf1-dependent genes are partially rescued by cip1{Delta} and cip2{Delta} 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.

{dagger}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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