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22 (23): 6256-6266

Copyright © 2003 by the European Molecular Biology Organization.

RNA-binding protein Csx1 mediates global control of gene expression in response to oxidative stress

Miguel A. Rodríguez-Gabriel1,2, Gavin Burns3, W.Hayes McDonald4, Victoria Martín1, John R. Yates, III4, Jürg Bähler3, and Paul Russell1,4

1 Department of Molecular Biology and 4 Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA and 3 The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK 2 Corresponding author e-mail: miguelr{at}scripps.edu

Abstract: Fission yeast Spc1 (Sty1), a stress-activated mitogen-activated protein kinase (MAPK) homologous to human p38, orchestrates global changes in gene expression in response to diverse forms of cytotoxic stress. This control is partly mediated through Atf1, a transcription factor homologous to human ATF2. How Spc1 controls Atf1, and how the cells tailor gene expression patterns to different forms of stress, are unknown. Here we describe Csx1, a novel protein crucial for survival of oxidative but not osmotic stress. Csx1 associates with and stabilizes atf1+ mRNA in response to oxidative stress. Csx1 controls expression of the majority of the genes induced by oxidative stress, including most of the genes regulated by Spc1 and Atf1. These studies reveal a novel mechanism controlling MAPK-regulated transcription factors and suggest how gene expression patterns can be customized to specific forms of stress. Csx1-like proteins in humans may perform similar tasks.

Key Words: Keywords: microarray/oxidative stress/post-transcriptional control of gene expression/RNA-binding protein/Schizosaccharomyces pombe

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