HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 19, 14113-14120, May 11, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/19/14113    most recent M701345200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Max, T. Articles by Svejstrup, J. Q. Search for Related Content PubMed PubMed Citation Articles by Max, T. Articles by Svejstrup, J. Q.

Hyperphosphorylation of the C-terminal Repeat Domain of RNA Polymerase II Facilitates Dissociation of Its Complex with Mediator^*

From the Clare Hall Laboratories, Cancer Research UK London Research Institute, Blanche Lane, South Mimms EN6 3LD, United Kingdom

The Mediator complex associates with RNA polymerase II (RNAPII) at least partly via the RNAPII C-terminal repeat domain (CTD). This association greatly stimulates the CTD kinase activity of general transcription factor TFIIH, and subsequent CTD phosphorylation is involved in triggering promoter clearance. Here, highly purified proteins and a protein dissociation assay were used to investigate whether the RNAPII·Mediator complex (holo-RNAPII) can be disrupted by CTD phosphorylation, thereby severing one of the bonds that stabilize promoter-associated initiation complexes. We report that CTD phosphorylation by the serine 5-specific TFIIH complex, or its kinase module TFIIK, is indeed sufficient to dissociate holo-RNAPII. Surprisingly, phosphorylation by the CTD serine 2-specific kinase CTDK1 also results in dissociation. Moreover, the Mediator-induced stimulation of CTD phosphorylation previously reported for TFIIH is also observed with CTDK1 kinase. An unrelated CTD-binding protein, Rsp5, is capable of stimulating this CTD kinase activity as well. These data shed new light on mechanisms that drive the RNAPII transcription cycle and suggest a mechanism for the enhancement of CTD kinase activity by the Mediator complex.

Received for publication, February 15, 2007 , and in revised form, March 21, 2007.

^* This work was supported by a generous in-house grant from Cancer Research UK (to J. Q. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed. Tel.: 44-1707-62-5960; Fax: 44-207-269-3801; E-mail: j.svejstrup{at}cancer.org.uk.

This article has been cited by other articles:

				O. Mikhaylova, M. L. Ignacak, T. J. Barankiewicz, S. V. Harbaugh, Y. Yi, P. H. Maxwell, M. Schneider, K. Van Geyte, P. Carmeliet, M. P. Revelo, et al. The von Hippel-Lindau Tumor Suppressor Protein and Egl-9-Type Proline Hydroxylases Regulate the Large Subunit of RNA Polymerase II in Response to Oxidative Stress Mol. Cell. Biol., April 15, 2008; 28(8): 2701 - 2717. [Abstract] [Full Text] [PDF]

				S. A. Shell, K. Martincic, J. Tran, and C. Milcarek Increased Phosphorylation of the Carboxyl-Terminal Domain of RNA Polymerase II and Loading of Polyadenylation and Cotranscriptional Factors Contribute to Regulation of the Ig Heavy Chain mRNA in Plasma Cells J. Immunol., December 1, 2007; 179(11): 7663 - 7673. [Abstract] [Full Text] [PDF]