title: The fission yeast stress-responsive MAPK pathway promotes meiosis via the phosphorylation of Pol II CTD in response to environmental and feedback cues.
abstract: The RRM-type RNA-binding protein Mei2 is a master regulator of meiosis in fission yeast, in which it stabilizes meiosis-specific mRNAs by blocking their destruction. Artificial activation of Mei2 can provoke the entire meiotic process, and it is suspected that Mei2 may do more than the stabilization of meiosis-specific mRNAs. In our current study using a new screening system, we show that Mei2 genetically interacts with subunits of CTDK-I, which phosphorylates serine-2 residues on the C-terminal domain of RNA polymerase II (Pol II CTD). Phosphorylation of CTD Ser-2 is essential to enable the robust transcription of ste11, which encodes an HMG-type transcription factor that regulates the expression of mei2 and other genes necessary for sexual development. CTD Ser-2 phosphorylation increases under nitrogen starvation, and the stress-responsive MAP kinase pathway, mediated by Wis1 MAPKK and Sty1 MAPK, is critical for this stress response. Sty1 phosphorylates Lsk1, the catalytic subunit of CTDK-I. Furthermore, a feedback loop stemming from activated Mei2 to Win1 and Wis4 MAPKKKs operates in this pathway and eventually enhances CTD Ser-2 phosphorylation and ste11 transcription. Hence, in addition to starting meiosis, Mei2 functions to reinforce the commitment to it, once cells have entered this process. This study also demonstrates clearly that the stress-responsive MAP kinase pathway can modulates gene expression through phosphorylation of Pol II CTD.
authors.affiliation: Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sukegawa
authors.forename: Akira
authors.initials: A
authors.lastname: Yamashita
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D015966:Gene Expression Regulation, Fungal; D008540:Meiosis / Q000235:genetics*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics*; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics; D012319:RNA Polymerase II / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D012568:Schizosaccharomyces / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C088896:mei2 protein, S pombe; C071596:ste11 protein, S pombe; D011494:Protein Kinases; C060137:carboxy-terminal domain kinase; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe; D020929:Mitogen-Activated Protein Kinase Kinases; C072068:wis1 protein, S pombe; D012319:RNA Polymerase II