KAP1 Recruitment of the 7SK snRNP Complex to Promoters Enables Transcription Elongation by RNA Polymerase II

Ryan P. McNamara, Jonathan E. Reeder, Elizabeth A. McMillan, Curtis W. Bacon, Jennifer L. McCann, Iván D'Orso

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

The transition from transcription initiation to elongation at promoters of primary response genes (PRGs) in metazoan cells is controlled by inducible transcription factors, which utilize P-TEFb to phosphorylate RNA polymerase II (Pol II) in response to stimuli. Prior to stimulation, a fraction of P-TEFb is recruited to promoter-proximal regions in a catalytically inactive state bound to the 7SK small nuclear ribonucleoprotein (snRNP) complex. However, it remains unclear how and why the 7SK snRNP is assembled at these sites. Here we report that the transcriptional regulator KAP1 continuously tethers the 7SK snRNP to PRG promoters to facilitate P-TEFb recruitment and productive elongation in response to stimulation. Remarkably, besides PRGs, genome-wide studies revealed that KAP1 and 7SK snRNP co-occupy most promoter-proximal regions containing paused Pol II. Collectively, we provide evidence of an unprecedented mechanism controlling 7SK snRNP delivery to promoter-proximal regions to facilitate "on-site" P-TEFb activation and Pol II elongation. McNamara et al. use a combination of biochemical approaches to identify KAP1 as an interactor of the 7SK snRNP complex. Using genomics, they found that the KAP1-7SK snRNP complex is recruited to most promoter-proximal regions containing paused RNA polymerase II to facilitate "on-site" P-TEFb activation and transcriptional pause release.

Original languageEnglish (US)
Pages (from-to)39-53
Number of pages15
JournalMolecular Cell
Volume61
Issue number1
DOIs
StatePublished - Jan 7 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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