Rpb4/7 facilitates RNA polymerase II CTD dephosphorylation
| Autor: | Francisco Navarro, Sergio Alonso-Aguado, Verónica Martínez-Fernández, Steven D. Hanes, Ana I. Garrido-Godino, Paula Allepuz-Fuster, Olga Calvo |
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| Přispěvatelé: | Ministerio de Ciencia e Innovación (España), Junta de Andalucía, National Institutes of Health (US), State University of New York, Ministerio de Educación y Ciencia (España) |
| Rok vydání: | 2014 |
| Předmět: |
Saccharomyces cerevisiae Proteins
RNA polymerase II Biology environment and public health 03 medical and health sciences 0302 clinical medicine Transcription (biology) Translational regulation Phosphoprotein Phosphatases Genetics 030304 developmental biology mRNA Cleavage and Polyadenylation Factors Peptidylprolyl isomerase 0303 health sciences Kinase Gene regulation Chromatin and Epigenetics Peptidylprolyl Isomerase Cyclin-Dependent Kinases Protein Structure Tertiary 3. Good health Chromatin NIMA-Interacting Peptidylprolyl Isomerase enzymes and coenzymes (carbohydrates) Biochemistry Mutation biology.protein Phosphorylation RNA Polymerase II CTD Protein Multimerization Protein Kinases 030217 neurology & neurosurgery |
| Zdroj: | Nucleic Acids Research Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | The Rpb4 and Rpb7 subunits of eukaryotic RNA polymerase II (RNAPII) participate in a variety of processes from transcription, DNA repair, mRNA export and decay, to translation regulation and stress response. However, their mechanism(s) of action remains unclear. Here, we show that the Rpb4/7 heterodimer in Saccharomyces cerevisiae plays a key role in controlling phosphorylation of the carboxy terminal domain (CTD) of the Rpb1 subunit of RNAPII. Proper phosphorylation of the CTD is critical for the synthesis and processing of RNAPII transcripts. Deletion of RPB4, and mutations that disrupt the integrity of Rpb4/7 or its recruitment to the RNAPII complex, increased phosphorylation of Ser2, Ser5, Ser7 and Thr4 within the CTD. RPB4 interacted genetically with genes encoding CTD phosphatases (SSU72, FCP1), CTD kinases (KIN28, CTK1, SRB10) and a prolyl isomerase that targets the CTD (ESS1). We show that Rpb4 is important for Ssu72 and Fcp1 phosphatases association, recruitment and/or accessibility to the CTD, and that this correlates strongly with Ser5P and Ser2P levels, respectively. Our data also suggest that Fcp1 is the Thr4P phosphatase in yeast. Based on these and other results, we suggest a model in which Rpb4/7 helps recruit and potentially stimulate the activity of CTD-modifying enzymes, a role that is central to RNAPII function. Spanish Ministry of Science and Innovation and FEDER [BFU 2009-07179 to O.C.; BFU2010-21975-03-02 to F.N.]; Junta de Andalucía [BIO258, PI10-CVI6521 to F.N.]; Upstate Medical University and National Institutes of Health [R01-GM055108 to S.D.H.]. Predoctoral fellowships from MEC [to I.G.-G.]; Junta de Andalucía [to V.M.-F.]. Funding for open access charge: Start-up funding from State University of New York, Upstate Medical University [to S.D.H.]. |
| Databáze: | OpenAIRE |
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