CDK9 inhibitors define elongation checkpoints at both ends of RNA polymerase II-transcribed genes
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English English |
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Nature Publishing Group
2015
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| Online Access: | http://irep.iium.edu.my/60432/ http://irep.iium.edu.my/60432/1/2015-NSMB.pdf http://irep.iium.edu.my/60432/7/60432_CDK9%20inhibitors%20define%20elongation_scopus.pdf |
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| author | Laitem, Clélia Zaborowska, Justyna Isa, Nur Firdaus Kufs, Johann Dienstbier, Martin Murphy, Shona |
| author_facet | Laitem, Clélia Zaborowska, Justyna Isa, Nur Firdaus Kufs, Johann Dienstbier, Martin Murphy, Shona |
| author_sort | Laitem, Clélia |
| building | IIUM Repository |
| collection | Online Access |
| description | 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 |
| first_indexed | 2025-11-14T16:53:58Z |
| format | Article |
| id | iium-60432 |
| institution | International Islamic University Malaysia |
| institution_category | Local University |
| language | English English |
| last_indexed | 2025-11-14T16:53:58Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | iium-604322017-12-26T10:07:39Z http://irep.iium.edu.my/60432/ CDK9 inhibitors define elongation checkpoints at both ends of RNA polymerase II-transcribed genes Laitem, Clélia Zaborowska, Justyna Isa, Nur Firdaus Kufs, Johann Dienstbier, Martin Murphy, Shona Q Science (General) R Medicine (General) 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 Nature Publishing Group 2015-05 Article PeerReviewed application/pdf en http://irep.iium.edu.my/60432/1/2015-NSMB.pdf application/pdf en http://irep.iium.edu.my/60432/7/60432_CDK9%20inhibitors%20define%20elongation_scopus.pdf 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 https://www.nature.com/articles/nsmb.3000 10.1038/nsmb.3000 |
| spellingShingle | Q Science (General) R Medicine (General) Laitem, Clélia Zaborowska, Justyna Isa, Nur Firdaus Kufs, Johann Dienstbier, Martin Murphy, Shona CDK9 inhibitors define elongation checkpoints at both ends of RNA polymerase II-transcribed genes |
| title | CDK9 inhibitors define elongation checkpoints at both ends of
RNA polymerase II-transcribed genes |
| title_full | CDK9 inhibitors define elongation checkpoints at both ends of
RNA polymerase II-transcribed genes |
| title_fullStr | CDK9 inhibitors define elongation checkpoints at both ends of
RNA polymerase II-transcribed genes |
| title_full_unstemmed | CDK9 inhibitors define elongation checkpoints at both ends of
RNA polymerase II-transcribed genes |
| title_short | CDK9 inhibitors define elongation checkpoints at both ends of
RNA polymerase II-transcribed genes |
| title_sort | cdk9 inhibitors define elongation checkpoints at both ends of
rna polymerase ii-transcribed genes |
| topic | Q Science (General) R Medicine (General) |
| url | http://irep.iium.edu.my/60432/ http://irep.iium.edu.my/60432/ http://irep.iium.edu.my/60432/ http://irep.iium.edu.my/60432/1/2015-NSMB.pdf http://irep.iium.edu.my/60432/7/60432_CDK9%20inhibitors%20define%20elongation_scopus.pdf |