RNA-binding protein Csx1 mediates global control of gene expression in response to oxidative stress.
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.
Rodríguez-Gabriel
Miguel A
MA
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. miguelr@scripps.edu
Burns
Gavin
G
McDonald
W Hayes
WH
Martín
Victoria
V
Yates
John R
JR
Bähler
Jürg
J
Russell
Paul
P
D005656:Fungal Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism*; D016254:Mutagenesis, Insertional; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000502:physiology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
D005656:Fungal Proteins; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors