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Molecular and Cellular Biology, September 2006, p. 6347-6356, Vol. 26, No. 17
0270-7306/06/$08.00+0 doi:10.1128/MCB.00286-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Department of Molecular Biology,1 Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037,2 The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom,3 Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain4
Received 15 February 2006/ Returned for modification 14 March 2006/ Accepted 16 June 2006
In the fission yeast Schizosaccharomyces pombe, oxidative stress triggers the activation of the Spc1/Sty1 mitogen-activated protein kinase, which in turn phosphorylates the Atf1/Pcr1 heterodimeric transcription factor to effect global changes in the patterns of gene expression. This transcriptional response is also controlled by Csx1, an RNA-binding protein that directly associates with and stabilizes atf1+ mRNA. Here we report the surprising observation that this response also requires Upf1, a component of the nonsense-mediated mRNA decay (NMD) system. Accordingly, upf1
and csx1
strains are similarly sensitive to oxidative stress, and the effects of the mutations are not additive, suggesting that Upf1 and Csx1 work in the same pathway to stabilize atf1+ mRNA during oxidative stress. Consistent with these observations, whole-genome expression profiling studies have shown that Upf1 controls the expression of more than 100 genes that are transcriptionally induced in response to oxidative stress, the large majority of which are also controlled by Atf1 and Csx1. The unexpected connection between an NMD factor and the oxidative stress response in fission yeast may provide important new clues about the physiological function of NMD in other species.
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