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

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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1093/nar/gkaa514

Authors

More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Pathology Dunn School
Role:
Author


Publisher:
Oxford University Press
Journal:
Nucleic Acids Research More from this journal
Volume:
48
Issue:
14
Pages:
7712-7727
Publication date:
2020-06-17
Acceptance date:
2020-06-03
DOI:
EISSN:
1362-4962
ISSN:
0305-1048


Language:
English
Keywords:
Pubs id:
1109128
Local pid:
pubs:1109128
Deposit date:
2020-06-04
ARK identifier:

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