Evidence map›Paper›PMID 25849141›Full record

ArticleNature structural & molecular biology2015

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

Clélia Laitem, Justyna Zaborowska, Nur F Isa, Johann Kufs, Martin Dienstbier, Shona Murphy

Abstract read
In one paragraph

Article in Nature structural & molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

90 citing papers in PubMed.

  1. Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026
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  18. mRNA initiation and termination are spatially coordinated.bioRxiv : the preprint server for biology · 2024
    Article
  19. Article
  20. Article

30 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Clélia LaitemSir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Justyna ZaborowskaSir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Nur F Isa1] Sir William Dunn School of Pathology, University of Oxford, Oxford, UK. [2] Department of Biotechnology, International Islamic University Malaysia, Pahang, Malaysia.
Johann KufsFaculty of Science, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany.
Martin DienstbierComputational Genomics Analysis and Training Programme, Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.ORCID 0000000151400002
Shona MurphySir William Dunn School of Pathology, University of Oxford, Oxford, UK.

Funding

Medical Research Council G0400653Medical Research Council G0900747Medical Research Council G0900747 91070Wellcome Trust 088542Wellcome Trust 088542/Z/09/ZWellcome Trust 090532/Z/09/ZWellcome Trust 092483Wellcome Trust 092483/Z/10/ZWellcome Trust 106134
6 · The paper itself

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 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.

Indexed as

Base SequenceCell Line, TumorCyclin-Dependent Kinase 9Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)HEK293 CellsHeLa CellsHumansPeptide Chain Elongation, TranslationalPromoter Regions, GeneticRNA InterferenceRNA Polymerase IIRNA, Small InterferingSequence Analysis, DNATranscription, GeneticCDK9 protein, humanCyclin-Dependent Kinase 9Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)RNA Polymerase IIRNA, Small Interfering

Identifiers

PMID25849141
PMCPMC4424039

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.