In vitro analysis of RNA polymerase II elongation complex dynamics

Genes Dev. 2019 May 1;33(9-10):578-589. doi: 10.1101/gad.324202.119. Epub 2019 Mar 7.

Abstract

RNA polymerase II elongation complexes (ECs) were assembled from nuclear extract on immobilized DNA templates and analyzed by quantitative mass spectrometry. Time-course experiments showed that initiation factor TFIIF can remain bound to early ECs, while levels of core elongation factors Spt4-Spt5, Paf1C, Spt6-Spn1, and Elf1 remain steady. Importantly, the dynamic phosphorylation patterns of the Rpb1 C-terminal domain (CTD) and the factors that recognize them change as a function of postinitiation time rather than distance elongated. Chemical inhibition of Kin28/Cdk7 in vitro blocks both Ser5 and Ser2 phosphorylation, affects initiation site choice, and inhibits elongation efficiency. EC components dependent on CTD phosphorylation include capping enzyme, cap-binding complex, Set2, and the polymerase-associated factor (PAF1) complex. By recapitulating many known features of in vivo elongation, this system reveals new details that clarify how EC-associated factors change at each step of transcription.

Keywords: Cdk7; DSIF; Paf1 complex; RNA polymerase II C-terminal domain (CTD); Spt6; transcription elongation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclin-Dependent Kinases / metabolism
  • Enzyme Activation
  • Peptide Elongation Factors / metabolism
  • Phosphorylation
  • Protein Kinases / metabolism
  • RNA Polymerase II / chemistry
  • RNA Polymerase II / metabolism*
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Peptide Elongation Factors
  • Saccharomyces cerevisiae Proteins
  • Protein Kinases
  • Cyclin-Dependent Kinases
  • Kin28 protein kinase, S cerevisiae
  • RNA Polymerase II