title: Cip1 and Cip2 are novel RNA-recognition-motif proteins that counteract Csx1 function during oxidative stress.
abstract: 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 cip1Delta cip2Delta 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 csx1Delta cells to oxidative stress and their inability to induce expression of Atf1-dependent genes are partially rescued by cip1Delta and cip2Delta 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.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Martín
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Rodríguez-Gabriel
authors.forename: W Hayes
authors.initials: WH
authors.lastname: McDonald
authors.forename: Stephen
authors.initials: S
authors.lastname: Watt
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Jürg
authors.initials: J
authors.lastname: Bähler
authors.forename: Paul
authors.initials: P
authors.lastname: Russell
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D015966:Gene Expression Regulation, Fungal; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000166:cytology / Q000187:drug effects; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: C510973:Cip1 protein, S pombe; C510974:Cip2 protein, S pombe; C494358:Csx1 protein, S pombe; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; D006861:Hydrogen Peroxide