CDK9 inhibitors define elongation checkpoints at both ends of RNA polymerase II-transcribed genes

Laitem, Clélia and Zaborowska, Justyna and Isa, Nur Firdaus and Kufs, Johann and Dienstbier, Martin and Murphy, Shona (2015) CDK9 inhibitors define elongation checkpoints at both ends of RNA polymerase II-transcribed genes. Nature Structural & Molecular Biology, 22 (5). pp. 396-403. ISSN 1545-9993 E-ISSN 1545-9985

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Abstract

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 (Homo sapiens) 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 a hithertounsuspected poly(A)-associated elongation checkpoint, which has major implications for the regulation of gene expression. Interestingly, the pattern of modification of the carboxyl-terminal domain (CTD) of pol II terminated at this novel checkpoint largely mirrors the pattern normally found downstream of the poly(A) site, suggesting common mechanisms of termination

Item Type:	Article (Journal)
Additional Information:	8298/60432
Uncontrolled Keywords:	CDK9 inhibitors; Elongation checkpoints; RNA polymerase II-transcribed genes
Subjects:	Q Science > Q Science (General) R Medicine > R Medicine (General)
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Science > Department of Biotechnology
Depositing User:	Dr Nur Firdaus Isa
Date Deposited:	26 Dec 2017 18:07
Last Modified:	26 Dec 2017 18:07
URI:	http://irep.iium.edu.my/id/eprint/60432

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