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

Tellier, M., Zaborowska, J., Caizzi, L., Mohammad, E., Velychko, T., Schwalb, B., et al. (2020). CDK12 globally stimulates RNA polymerase II transcription elongation and carboxyl-terminal domain phosphorylation. Nucleic Acids Research, 48(14), 7712-7727. doi:10.1093/nar/gkaa514.

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Tellier, M., Author
Zaborowska, J., Author
Caizzi, L.1, Author              
Mohammad, E.1, Author              
Velychko, T.1, Author              
Schwalb, B.1, Author              
Ferrer-Vicens, I., Author
Blears, D., Author
Nojima, T., Author
Cramer, P.1, Author              
Murphy, S., Author
Affiliations:
1Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1863498              

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 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.

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Language(s): eng - English
 Dates: 2020-06-172020-08-20
 Publication Status: Published in print
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 Rev. Type: Peer
 Identifiers: DOI: 10.1093/nar/gkaa514
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Title: Nucleic Acids Research
Source Genre: Journal
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Pages: - Volume / Issue: 48 (14) Sequence Number: - Start / End Page: 7712 - 7727 Identifier: -