A conserved Mediator-CDK8 kinase module association regulates Mediator-RNA polymerase II interaction.

Abstract:

:The CDK8 kinase module (CKM) is a conserved, dissociable Mediator subcomplex whose component subunits were genetically linked to the RNA polymerase II (RNAPII) C-terminal domain (CTD) and individually recognized as transcriptional repressors before Mediator was identified as a pre-eminent complex in eukaryotic transcription regulation. We used macromolecular EM and biochemistry to investigate the subunit organization, structure and Mediator interaction of the Saccharomyces cerevisiae CKM. We found that interaction of the CKM with Mediator's middle module interferes with CTD-dependent RNAPII binding to a previously unknown middle-module CTD-binding site and with the holoenzyme formation process. Taken together, our results reveal the basis for CKM repression, clarify the origin of the connection between CKM subunits and the CTD and suggest that a combination of competitive interactions and conformational changes that facilitate holoenzyme formation underlie the mechanism of transcription regulation by Mediator.

journal_name

Nat Struct Mol Biol

authors

Tsai KL,Sato S,Tomomori-Sato C,Conaway RC,Conaway JW,Asturias FJ

doi

10.1038/nsmb.2549

subject

Has Abstract

pub_date

2013-05-01 00:00:00

pages

611-9

issue

5

eissn

1545-9993

issn

1545-9985

pii

nsmb.2549

journal_volume

20

pub_type

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