Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Transcription through early-elongation checkpoints requires phosphorylation of negative transcription elongation factors (NTEFs) by the cyclin-dependent kinase (CDK) 9. Using CDK9 inhibitors and global run-on sequencing (GRO-seq), we have mapped CDK9 inhibitor-sensitive checkpoints genome wide in human cells. Our data indicate that early-elongation checkpoints are a general feature of RNA polymerase (pol) II-transcribed human genes and occur independently of polymerase stalling. Pol II that has negotiated the early-elongation checkpoint can elongate in the presence of inhibitors but, remarkably, terminates transcription prematurely close to the terminal polyadenylation (poly(A)) site. Our analysis has revealed an unexpected poly(A)-associated elongation checkpoint, which has major implications for the regulation of gene expression. Interestingly, the pattern of modification of the C-terminal domain of pol II terminated at this new checkpoint largely mirrors the pattern normally found downstream of the poly(A) site, thus suggesting common mechanisms of termination.

Original publication

DOI

10.1038/nsmb.3000

Type

Journal article

Journal

Nat Struct Mol Biol

Publication Date

05/2015

Volume

22

Pages

396 - 403

Keywords

Base Sequence, Cell Line, Tumor, Cyclin-Dependent Kinase 9, Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating), HEK293 Cells, HeLa Cells, Humans, Peptide Chain Elongation, Translational, Promoter Regions, Genetic, RNA Interference, RNA Polymerase II, RNA, Small Interfering, Sequence Analysis, DNA, Transcription, Genetic