Skip to main content
PMC home page
Genetics logoLink to Genetics
. 2004 May;167(1):93–105. doi: 10.1534/genetics.167.1.93

Genetic interactions with C-terminal domain (CTD) kinases and the CTD of RNA Pol II suggest a role for ESS1 in transcription initiation and elongation in Saccharomyces cerevisiae.

Cathy B Wilcox 1, Anne Rossettini 1, Steven D Hanes 1
PMCID: PMC1470855  PMID: 15166139

Abstract

Ess1 is an essential prolyl isomerase that binds the C-terminal domain (CTD) of Rpb1, the large subunit of RNA polymerase II. Ess1 is proposed to control transcription by isomerizing phospho-Ser-Pro peptide bonds within the CTD repeat. To determine which step(s) in the transcription cycle might require Ess1, we examined genetic interactions between ESS1 and genes encoding the known CTD kinases (KIN28, CTK1, BUR1, and SRB10). Although genetic interactions were identified between ESS1 and all four kinases, the clearest interactions were with CTK1 and SRB10. Reduced dosage of CTK1 rescued the growth defect of ess1(ts) mutants, while overexpression of CTK1 enhanced the growth defects of ess1(ts) mutants. Deletion of SRB10 suppressed ess1(ts) and ess1Delta mutants. The interactions suggest that Ess1 opposes the functions of these kinases, which are thought to function in preinitiation and elongation. Using a series of CTD substitution alleles, we also identified Ser5-Pro6 as a potential target for Ess1 isomerization within the first "half" of the CTD repeats. On the basis of the results, we suggest a model in which Ess1-directed conformational changes promote dephosphorylation of Ser5 to stimulate preinitiation complex formation and, later, to inhibit elongation.

Full Text

The Full Text of this article is available as a PDF (474.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akhtar A., Faye G., Bentley D. L. Distinct activated and non-activated RNA polymerase II complexes in yeast. EMBO J. 1996 Sep 2;15(17):4654–4664. [PMC free article] [PubMed] [Google Scholar]
  2. Archambault J., Chambers R. S., Kobor M. S., Ho Y., Cartier M., Bolotin D., Andrews B., Kane C. M., Greenblatt J. An essential component of a C-terminal domain phosphatase that interacts with transcription factor IIF in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14300–14305. doi: 10.1073/pnas.94.26.14300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arévalo-Rodríguez M., Cardenas M. E., Wu X., Hanes S. D., Heitman J. Cyclophilin A and Ess1 interact with and regulate silencing by the Sin3-Rpd3 histone deacetylase. EMBO J. 2000 Jul 17;19(14):3739–3749. doi: 10.1093/emboj/19.14.3739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chi Y., Huddleston M. J., Zhang X., Young R. A., Annan R. S., Carr S. A., Deshaies R. J. Negative regulation of Gcn4 and Msn2 transcription factors by Srb10 cyclin-dependent kinase. Genes Dev. 2001 May 1;15(9):1078–1092. doi: 10.1101/gad.867501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cho E. J., Kobor M. S., Kim M., Greenblatt J., Buratowski S. Opposing effects of Ctk1 kinase and Fcp1 phosphatase at Ser 2 of the RNA polymerase II C-terminal domain. Genes Dev. 2001 Dec 15;15(24):3319–3329. doi: 10.1101/gad.935901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Christianson T. W., Sikorski R. S., Dante M., Shero J. H., Hieter P. Multifunctional yeast high-copy-number shuttle vectors. Gene. 1992 Jan 2;110(1):119–122. doi: 10.1016/0378-1119(92)90454-w. [DOI] [PubMed] [Google Scholar]
  7. Cismowski M. J., Laff G. M., Solomon M. J., Reed S. I. KIN28 encodes a C-terminal domain kinase that controls mRNA transcription in Saccharomyces cerevisiae but lacks cyclin-dependent kinase-activating kinase (CAK) activity. Mol Cell Biol. 1995 Jun;15(6):2983–2992. doi: 10.1128/mcb.15.6.2983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Conrad N. K., Wilson S. M., Steinmetz E. J., Patturajan M., Brow D. A., Swanson M. S., Corden J. L. A yeast heterogeneous nuclear ribonucleoprotein complex associated with RNA polymerase II. Genetics. 2000 Feb;154(2):557–571. doi: 10.1093/genetics/154.2.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Crenshaw D. G., Yang J., Means A. R., Kornbluth S. The mitotic peptidyl-prolyl isomerase, Pin1, interacts with Cdc25 and Plx1. EMBO J. 1998 Aug 10;17(5):1315–1327. doi: 10.1093/emboj/17.5.1315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Devasahayam Gina, Chaturvedi Vishnu, Hanes Steven D. The Ess1 prolyl isomerase is required for growth and morphogenetic switching in Candida albicans. Genetics. 2002 Jan;160(1):37–48. doi: 10.1093/genetics/160.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Giaever Guri, Chu Angela M., Ni Li, Connelly Carla, Riles Linda, Véronneau Steeve, Dow Sally, Lucau-Danila Ankuta, Anderson Keith, André Bruno. Functional profiling of the Saccharomyces cerevisiae genome. Nature. 2002 Jul 25;418(6896):387–391. doi: 10.1038/nature00935. [DOI] [PubMed] [Google Scholar]
  12. Hanes S. D., Shank P. R., Bostian K. A. Sequence and mutational analysis of ESS1, a gene essential for growth in Saccharomyces cerevisiae. Yeast. 1989 Jan-Feb;5(1):55–72. doi: 10.1002/yea.320050108. [DOI] [PubMed] [Google Scholar]
  13. Hani J., Stumpf G., Domdey H. PTF1 encodes an essential protein in Saccharomyces cerevisiae, which shows strong homology with a new putative family of PPIases. FEBS Lett. 1995 May 29;365(2-3):198–202. doi: 10.1016/0014-5793(95)00471-k. [DOI] [PubMed] [Google Scholar]
  14. Hengartner C. J., Myer V. E., Liao S. M., Wilson C. J., Koh S. S., Young R. A. Temporal regulation of RNA polymerase II by Srb10 and Kin28 cyclin-dependent kinases. Mol Cell. 1998 Jul;2(1):43–53. doi: 10.1016/s1097-2765(00)80112-4. [DOI] [PubMed] [Google Scholar]
  15. Hirose Y., Manley J. L. RNA polymerase II and the integration of nuclear events. Genes Dev. 2000 Jun 15;14(12):1415–1429. [PubMed] [Google Scholar]
  16. Holstege F. C., Jennings E. G., Wyrick J. J., Lee T. I., Hengartner C. J., Green M. R., Golub T. R., Lander E. S., Young R. A. Dissecting the regulatory circuitry of a eukaryotic genome. Cell. 1998 Nov 25;95(5):717–728. doi: 10.1016/s0092-8674(00)81641-4. [DOI] [PubMed] [Google Scholar]
  17. Keogh Michael-Christopher, Podolny Vladimir, Buratowski Stephen. Bur1 kinase is required for efficient transcription elongation by RNA polymerase II. Mol Cell Biol. 2003 Oct;23(19):7005–7018. doi: 10.1128/MCB.23.19.7005-7018.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kimmelman J., Kaldis P., Hengartner C. J., Laff G. M., Koh S. S., Young R. A., Solomon M. J. Activating phosphorylation of the Kin28p subunit of yeast TFIIH by Cak1p. Mol Cell Biol. 1999 Jul;19(7):4774–4787. doi: 10.1128/mcb.19.7.4774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kobor M. S., Archambault J., Lester W., Holstege F. C., Gileadi O., Jansma D. B., Jennings E. G., Kouyoumdjian F., Davidson A. R., Young R. A. An unusual eukaryotic protein phosphatase required for transcription by RNA polymerase II and CTD dephosphorylation in S. cerevisiae. Mol Cell. 1999 Jul;4(1):55–62. doi: 10.1016/s1097-2765(00)80187-2. [DOI] [PubMed] [Google Scholar]
  20. Komarnitsky P., Cho E. J., Buratowski S. Different phosphorylated forms of RNA polymerase II and associated mRNA processing factors during transcription. Genes Dev. 2000 Oct 1;14(19):2452–2460. doi: 10.1101/gad.824700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Laybourn P. J., Dahmus M. E. Transcription-dependent structural changes in the C-terminal domain of mammalian RNA polymerase subunit IIa/o. J Biol Chem. 1989 Apr 25;264(12):6693–6698. [PubMed] [Google Scholar]
  22. Lee J. M., Greenleaf A. L. CTD kinase large subunit is encoded by CTK1, a gene required for normal growth of Saccharomyces cerevisiae. Gene Expr. 1991 May;1(2):149–167. [PMC free article] [PubMed] [Google Scholar]
  23. Lee J. M., Greenleaf A. L. Modulation of RNA polymerase II elongation efficiency by C-terminal heptapeptide repeat domain kinase I. J Biol Chem. 1997 Apr 25;272(17):10990–10993. doi: 10.1074/jbc.272.17.10990. [DOI] [PubMed] [Google Scholar]
  24. Liao S. M., Zhang J., Jeffery D. A., Koleske A. J., Thompson C. M., Chao D. M., Viljoen M., van Vuuren H. J., Young R. A. A kinase-cyclin pair in the RNA polymerase II holoenzyme. Nature. 1995 Mar 9;374(6518):193–196. doi: 10.1038/374193a0. [DOI] [PubMed] [Google Scholar]
  25. Lin Patrick S., Marshall Nicholas F., Dahmus Michael E. CTD phosphatase: role in RNA polymerase II cycling and the regulation of transcript elongation. Prog Nucleic Acid Res Mol Biol. 2002;72:333–365. doi: 10.1016/s0079-6603(02)72074-6. [DOI] [PubMed] [Google Scholar]
  26. Lorenz M. C., Heitman J. Regulators of pseudohyphal differentiation in Saccharomyces cerevisiae identified through multicopy suppressor analysis in ammonium permease mutant strains. Genetics. 1998 Dec;150(4):1443–1457. doi: 10.1093/genetics/150.4.1443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lu K. P., Hanes S. D., Hunter T. A human peptidyl-prolyl isomerase essential for regulation of mitosis. Nature. 1996 Apr 11;380(6574):544–547. doi: 10.1038/380544a0. [DOI] [PubMed] [Google Scholar]
  28. Majello B., Napolitano G., Giordano A., Lania L. Transcriptional regulation by targeted recruitment of cyclin-dependent CDK9 kinase in vivo. Oncogene. 1999 Aug 12;18(32):4598–4605. doi: 10.1038/sj.onc.1202822. [DOI] [PubMed] [Google Scholar]
  29. Morris D. P., Phatnani H. P., Greenleaf A. L. Phospho-carboxyl-terminal domain binding and the role of a prolyl isomerase in pre-mRNA 3'-End formation. J Biol Chem. 1999 Oct 29;274(44):31583–31587. doi: 10.1074/jbc.274.44.31583. [DOI] [PubMed] [Google Scholar]
  30. Murray S., Udupa R., Yao S., Hartzog G., Prelich G. Phosphorylation of the RNA polymerase II carboxy-terminal domain by the Bur1 cyclin-dependent kinase. Mol Cell Biol. 2001 Jul;21(13):4089–4096. doi: 10.1128/MCB.21.13.4089-4096.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Patturajan M., Conrad N. K., Bregman D. B., Corden J. L. Yeast carboxyl-terminal domain kinase I positively and negatively regulates RNA polymerase II carboxyl-terminal domain phosphorylation. J Biol Chem. 1999 Sep 24;274(39):27823–27828. doi: 10.1074/jbc.274.39.27823. [DOI] [PubMed] [Google Scholar]
  32. Ramanathan Y., Rajpara S. M., Reza S. M., Lees E., Shuman S., Mathews M. B., Pe'ery T. Three RNA polymerase II carboxyl-terminal domain kinases display distinct substrate preferences. J Biol Chem. 2001 Jan 16;276(14):10913–10920. doi: 10.1074/jbc.M010975200. [DOI] [PubMed] [Google Scholar]
  33. Rodriguez C. R., Cho E. J., Keogh M. C., Moore C. L., Greenleaf A. L., Buratowski S. Kin28, the TFIIH-associated carboxy-terminal domain kinase, facilitates the recruitment of mRNA processing machinery to RNA polymerase II. Mol Cell Biol. 2000 Jan;20(1):104–112. doi: 10.1128/mcb.20.1.104-112.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Schiene C., Fischer G. Enzymes that catalyse the restructuring of proteins. Curr Opin Struct Biol. 2000 Feb;10(1):40–45. doi: 10.1016/s0959-440x(99)00046-9. [DOI] [PubMed] [Google Scholar]
  35. Shen M., Stukenberg P. T., Kirschner M. W., Lu K. P. The essential mitotic peptidyl-prolyl isomerase Pin1 binds and regulates mitosis-specific phosphoproteins. Genes Dev. 1998 Mar 1;12(5):706–720. doi: 10.1101/gad.12.5.706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Skaar David A., Greenleaf Arno L. The RNA polymerase II CTD kinase CTDK-I affects pre-mRNA 3' cleavage/polyadenylation through the processing component Pti1p. Mol Cell. 2002 Dec;10(6):1429–1439. doi: 10.1016/s1097-2765(02)00731-1. [DOI] [PubMed] [Google Scholar]
  37. Wach A., Brachat A., Pöhlmann R., Philippsen P. New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae. Yeast. 1994 Dec;10(13):1793–1808. doi: 10.1002/yea.320101310. [DOI] [PubMed] [Google Scholar]
  38. West M. L., Corden J. L. Construction and analysis of yeast RNA polymerase II CTD deletion and substitution mutations. Genetics. 1995 Aug;140(4):1223–1233. doi: 10.1093/genetics/140.4.1223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Wu X., Chang A., Sudol M., Hanes S. D. Genetic interactions between the ESS1 prolyl-isomerase and the RSP5 ubiquitin ligase reveal opposing effects on RNA polymerase II function. Curr Genet. 2001 Dec;40(4):234–242. doi: 10.1007/s00294-001-0257-8. [DOI] [PubMed] [Google Scholar]
  40. Wu X., Wilcox C. B., Devasahayam G., Hackett R. L., Arévalo-Rodríguez M., Cardenas M. E., Heitman J., Hanes S. D. The Ess1 prolyl isomerase is linked to chromatin remodeling complexes and the general transcription machinery. EMBO J. 2000 Jul 17;19(14):3727–3738. doi: 10.1093/emboj/19.14.3727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wu Xiaoyun, Rossettini Anne, Hanes Steven D. The ESS1 prolyl isomerase and its suppressor BYE1 interact with RNA pol II to inhibit transcription elongation in Saccharomyces cerevisiae. Genetics. 2003 Dec;165(4):1687–1702. doi: 10.1093/genetics/165.4.1687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Yaffe M. B., Schutkowski M., Shen M., Zhou X. Z., Stukenberg P. T., Rahfeld J. U., Xu J., Kuang J., Kirschner M. W., Fischer G. Sequence-specific and phosphorylation-dependent proline isomerization: a potential mitotic regulatory mechanism. Science. 1997 Dec 12;278(5345):1957–1960. doi: 10.1126/science.278.5345.1957. [DOI] [PubMed] [Google Scholar]
  43. Yuryev A., Corden J. L. Suppression analysis reveals a functional difference between the serines in positions two and five in the consensus sequence of the C-terminal domain of yeast RNA polymerase II. Genetics. 1996 Jun;143(2):661–671. doi: 10.1093/genetics/143.2.661. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES