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  A BRD4-mediated elongation control point primes transcribing RNA polymerase II for 3′-processing and termination

Arnold, M., Bressin, A., Jasnovidova, O., Meierhofer, D., & Mayer, A. (2021). A BRD4-mediated elongation control point primes transcribing RNA polymerase II for 3′-processing and termination. Molecular Cell, 81(17): e13, pp. 3589-3603. doi:10.1016/j.molcel.2021.06.026.

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 Creators:
Arnold, Mirjam1, Author           
Bressin, Annkatrin1, Author           
Jasnovidova, Olga1, Author           
Meierhofer, David2, Author           
Mayer, Andreas1, Author           
Affiliations:
1Nascent Transcription and Cell Differentiation (Andreas Mayer), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2385699              
2Mass Spectrometry (Head: David Meierhofer), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479669              

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Free keywords: RNA polymerase II BRD4 transcription termination readthrough 3’-RNA processing transcription elongation BET proteins promoter-proximal pausing checkpoint PAF1 complex
 Abstract: Transcription elongation has emerged as a regulatory hub in gene expression of metazoans. A major control point occurs during early elongation before RNA polymerase II (Pol II) is released into productive elongation. Prior research has linked BRD4 with transcription elongation. Here, we use rapid BET protein and BRD4-selective degradation along with quantitative genome-wide approaches to investigate direct functions of BRD4 in Pol II transcription regulation. Notably, as an immediate consequence of acute BRD4 loss, promoter-proximal pause release is impaired, and transcriptionally engaged Pol II past this checkpoint undergoes readthrough transcription. An integrated proteome-wide analysis uncovers elongation and 3′-RNA processing factors as core BRD4 interactors. BRD4 ablation disrupts the recruitment of general 3′-RNA processing factors at the 5′-control region, which correlates with RNA cleavage and termination defects. These studies, performed in human cells, reveal a BRD4-mediated checkpoint and begin to establish a molecular link between 5′-elongation control and 3′-RNA processing.

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Language(s): eng - English
 Dates: 2021-06-222021-07-282021-09-02
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.molcel.2021.06.026
 Degree: -

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Title: Molecular Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 81 (17) Sequence Number: e13 Start / End Page: 3589 - 3603 Identifier: ISSN: 1097-2765
CoNE: https://pure.mpg.de/cone/journals/resource/954925610929