CDK12 globally stimulates RNA polymerase II transcription elongation and carboxyl-terminal domain phosphorylation

Michael Tellier, Justyna Zaborowska, Livia Caizzi, Eusra Mohammad, Taras Velychko, Björn Schwalb, Ivan Ferrer-Vicens, Daniel Blears, Takayuki Nojima, Patrick Cramer, Shona Murphy

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Cyclin-dependent kinase 12 (CDK12) phosphorylates the carboxyl-terminal domain (CTD) of RNA polymerase II (pol II) but its roles in transcription beyond the expression of DNA damage response genes remain unclear. Here, we have used TT-seq and mNET-seq to monitor the direct effects of rapid CDK12 inhibition on transcription activity and CTD phosphorylation in human cells. CDK12 inhibition causes a genome-wide defect in transcription elongation and a global reduction of CTD Ser2 and Ser5 phosphorylation. The elongation defect is explained by the loss of the elongation factors LEO1 and CDC73, part of PAF1 complex, and SPT6 from the newly-elongating pol II. Our results indicate that CDK12 is a general activator of pol II transcription elongation and indicate that it targets both Ser2 and Ser5 residues of the pol II CTD.

Original languageEnglish
Pages (from-to)7712-7727
Number of pages16
JournalNucleic acids research
Volume48
Issue number14
DOIs
Publication statusPublished - Aug 20 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics

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