Transcription factors mediate the enzymatic disassembly of promoter-bound 7sk snrnp to locally recruit p-tefb for transcription elongation

RyanP McNamara, JenniferL McCann, Swapna Aravind Gudipaty, Iván D'Orso

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

The transition from transcription initiation into elongation is controlled by transcription factors, which recruit positive transcription elongation factor b (P-TEFb) to promoters to phosphorylate RNA polymerase II. A fraction of P-TEFb is recruited as part of the inhibitory 7SK small nuclear ribonucleoprotein particle (snRNP), which inactivates the kinase and prevents elongation. However, it is unclear how P-TEFb is captured from the promoter-bound 7SK snRNP to activate elongation. Here, we describe a mechanism by which transcription factors mediate the enzymatic release of P-TEFb from the 7SK snRNP at promoters to trigger activation in a gene-specific manner. We demonstrate that Tat recruits PPM1G/PP2Cγ to locally disassemble P-TEFb from the 7SK snRNP at the HIV promoter via dephosphorylation of the kinase T loop. Similar to Tat, nuclear factor (NF)-κB recruits PPM1G in a stimulus-dependent manner to activate elongation at inflammatory-responsive genes. Recruitment of PPM1G to promoter-assembled 7SK snRNP provides a paradigm for rapid gene activation through transcriptional pause release.

Original languageEnglish (US)
Pages (from-to)1256-1268
Number of pages13
JournalCell Reports
Volume5
Issue number5
DOIs
StatePublished - Dec 12 2013

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Small Nuclear Ribonucleoproteins
Peptide Elongation Factors
Transcription
Elongation
Transcription Factors
Genes
Phosphotransferases
Chemical activation
RNA Polymerase II
Transcriptional Activation
HIV

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Transcription factors mediate the enzymatic disassembly of promoter-bound 7sk snrnp to locally recruit p-tefb for transcription elongation. / McNamara, RyanP; McCann, JenniferL; Gudipaty, Swapna Aravind; D'Orso, Iván.

In: Cell Reports, Vol. 5, No. 5, 12.12.2013, p. 1256-1268.

Research output: Contribution to journalArticle

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