Bur1 Kinase is Required for Efficient Transcription Elongation by RNA Polymerase II

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2003 Sep 16

PMID 12972617

Citations 96

Authors

Michael-Christopher Keogh

Vladimir Podolny

Stephen Buratowski

Affiliations

Soon will be listed here.

Abstract

The Saccharomyces cerevisiae cyclin-dependent kinase (CDK) Bur1 (Sgv1) may be homologous to mammalian Cdk9, which functions in transcriptional elongation. Although Bur1 can phosphorylate the Rpb1 carboxy-terminal domain (CTD) kinase in vitro, it has no strong specificity within the consensus heptapeptide YSPTSPS for Ser2 or Ser5. BUR1 mutants are sensitive to the drugs 6-azauracil and mycophenolic acid and interact genetically with the elongation factors Ctk1 and Spt5. Chromatin immunoprecipitation experiments show that Bur1 and its cyclin partner Bur2 are recruited to transcription elongation complexes, cross-linking to actively transcribing genes. Interestingly, Bur1 shows reduced cross-linking to transcribed regions downstream of polyadenylation sites. In addition, bur1 mutant strains have a reduced cross-linking ratio of RNA polymerase II at the 3' end of genes relative to promoter regions. Phosphorylation of CTD serines 2 and 5 appears normal in mutant cells, suggesting that Bur1 is not a significant source of cotranscriptional Rpb1 phosphorylation. These results show that Bur1 functions in transcription elongation but may phosphorylate a substrate other than the CTD.

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References

Jeffrey P, Russo A, Polyak K, Gibbs E, Hurwitz J, Massague J . Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex. Nature. 1995; 376(6538):313-20. DOI: 10.1038/376313a0. View

Zhou M, Halanski M, Radonovich M, Kashanchi F, Peng J, Price D . Tat modifies the activity of CDK9 to phosphorylate serine 5 of the RNA polymerase II carboxyl-terminal domain during human immunodeficiency virus type 1 transcription. Mol Cell Biol. 2000; 20(14):5077-86. PMC: 85957. DOI: 10.1128/MCB.20.14.5077-5086.2000. View

Russo A, Jeffrey P, Pavletich N . Structural basis of cyclin-dependent kinase activation by phosphorylation. Nat Struct Biol. 1996; 3(8):696-700. DOI: 10.1038/nsb0896-696. View

Squazzo S, Costa P, Lindstrom D, Kumer K, Simic R, Jennings J . The Paf1 complex physically and functionally associates with transcription elongation factors in vivo. EMBO J. 2002; 21(7):1764-74. PMC: 125365. DOI: 10.1093/emboj/21.7.1764. View

Ramanathan Y, Rajpara S, Reza S, Lees E, Shuman S, Mathews M . Three RNA polymerase II carboxyl-terminal domain kinases display distinct substrate preferences. J Biol Chem. 2001; 276(14):10913-20. DOI: 10.1074/jbc.M010975200. View

Solomon M, Kaldis P . Regulation of CDKs by phosphorylation. Results Probl Cell Differ. 1998; 22:79-109. DOI: 10.1007/978-3-540-69686-5_4. View

Keogh M, Cho E, Podolny V, Buratowski S . Kin28 is found within TFIIH and a Kin28-Ccl1-Tfb3 trimer complex with differential sensitivities to T-loop phosphorylation. Mol Cell Biol. 2002; 22(5):1288-97. PMC: 134711. DOI: 10.1128/MCB.22.5.1288-1297.2002. View

Cho E, Takagi T, Moore C, Buratowski S . mRNA capping enzyme is recruited to the transcription complex by phosphorylation of the RNA polymerase II carboxy-terminal domain. Genes Dev. 1998; 11(24):3319-26. PMC: 316800. DOI: 10.1101/gad.11.24.3319. View

Akoulitchev S, Chuikov S, Reinberg D . TFIIH is negatively regulated by cdk8-containing mediator complexes. Nature. 2000; 407(6800):102-6. DOI: 10.1038/35024111. View

10.

Dahmus M . Reversible phosphorylation of the C-terminal domain of RNA polymerase II. J Biol Chem. 1996; 271(32):19009-12. DOI: 10.1074/jbc.271.32.19009. View

11.

Schroeder S, Schwer B, Shuman S, Bentley D . Dynamic association of capping enzymes with transcribing RNA polymerase II. Genes Dev. 2000; 14(19):2435-40. PMC: 316982. DOI: 10.1101/gad.836300. View

12.

Yao S, NEIMAN A, Prelich G . BUR1 and BUR2 encode a divergent cyclin-dependent kinase-cyclin complex important for transcription in vivo. Mol Cell Biol. 2000; 20(19):7080-7. PMC: 86248. DOI: 10.1128/MCB.20.19.7080-7087.2000. View

13.

Lennon 3rd J, Wind M, Saunders L, Hock M, Reines D . Mutations in RNA polymerase II and elongation factor SII severely reduce mRNA levels in Saccharomyces cerevisiae. Mol Cell Biol. 1998; 18(10):5771-9. PMC: 109163. DOI: 10.1128/MCB.18.10.5771. View

14.

Happel A, Swanson M, Winston F . The SNF2, SNF5 and SNF6 genes are required for Ty transcription in Saccharomyces cerevisiae. Genetics. 1991; 128(1):69-77. PMC: 1204454. DOI: 10.1093/genetics/128.1.69. View

15.

Orlando V . Mapping chromosomal proteins in vivo by formaldehyde-crosslinked-chromatin immunoprecipitation. Trends Biochem Sci. 2000; 25(3):99-104. DOI: 10.1016/s0968-0004(99)01535-2. View

16.

Yao S, Prelich G . Activation of the Bur1-Bur2 cyclin-dependent kinase complex by Cak1. Mol Cell Biol. 2002; 22(19):6750-8. PMC: 134033. DOI: 10.1128/MCB.22.19.6750-6758.2002. View

17.

Ranish J, Yi E, Leslie D, Purvine S, Goodlett D, Eng J . The study of macromolecular complexes by quantitative proteomics. Nat Genet. 2003; 33(3):349-55. DOI: 10.1038/ng1101. View

18.

Krogan N, Kim M, Ahn S, Zhong G, Kobor M, Cagney G . RNA polymerase II elongation factors of Saccharomyces cerevisiae: a targeted proteomics approach. Mol Cell Biol. 2002; 22(20):6979-92. PMC: 139818. DOI: 10.1128/MCB.22.20.6979-6992.2002. View

19.

Lavoie S, Albert A, Handa H, Vincent M, Bensaude O . The peptidyl-prolyl isomerase Pin1 interacts with hSpt5 phosphorylated by Cdk9. J Mol Biol. 2001; 312(4):675-85. DOI: 10.1006/jmbi.2001.4991. View

20.

Lee J, Greenleaf A . CTD kinase large subunit is encoded by CTK1, a gene required for normal growth of Saccharomyces cerevisiae. Gene Expr. 1991; 1(2):149-67. PMC: 5952209. View