PAF1, a Molecular Regulator of Promoter-Proximal Pausing by RNA Polymerase II

Fei Xavier Chen, Ashley R. Woodfin, Alessandro Gardini, Ryan A. Rickels, Stacy A. Marshall, Edwin R. Smith, Ramin Shiekhattar, Ali Shilatifard*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

Summary The control of promoter-proximal pausing and the release of RNA polymerase II (Pol II) is a widely used mechanism for regulating gene expression in metazoans, especially for genes that respond to environmental and developmental cues. Here, we identify that Pol-II-associated factor 1 (PAF1) possesses an evolutionarily conserved function in metazoans in the regulation of promoter-proximal pausing. Reduction in PAF1 levels leads to an increased release of paused Pol II into gene bodies at thousands of genes. PAF1 depletion results in increased nascent and mature transcripts and increased levels of phosphorylation of Pol II's C-terminal domain on serine 2 (Ser2P). These changes can be explained by the recruitment of the Ser2P kinase super elongation complex (SEC) effecting increased release of paused Pol II into productive elongation, thus establishing PAF1 as a regulator of promoter-proximal pausing by Pol II.

Original languageEnglish (US)
Pages (from-to)1003-1015
Number of pages13
JournalCell
Volume162
Issue number5
DOIs
StatePublished - Aug 27 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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