P-TEFb Activation by RBM7 Shapes a Pro-survival Transcriptional Response to Genotoxic Stress

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Bugai , A , Quaresma , A J C , Friedel , C C , Lenasi , T , Düster , R , Sibley , C R , Fuginaga , K , Kukanja , P , Hennig , T , Blasius , M , Geyer , M , Ule , J , Dölken , L & Barboric , M 2019 , ' P-TEFb Activation by RBM7 Shapes a Pro-survival Transcriptional Response to Genotoxic Stress ' , Molecular Cell , vol. 74 , no. 2 , pp. 254-+ . https://doi.org/10.1016/j.molcel.2019.01.033

Title: P-TEFb Activation by RBM7 Shapes a Pro-survival Transcriptional Response to Genotoxic Stress
Author: Bugai, Andrii; Quaresma, Alexandre J. C.; Friedel, Caroline C.; Lenasi, Tina; Düster, Robert; Sibley, Christopher R.; Fuginaga, Koh; Kukanja, Petra; Hennig, Thomas; Blasius, Melanie; Geyer, Matthias; Ule, Jernej; Dölken, Lars; Barboric, Matjaz
Contributor: University of Helsinki, Department of Biochemistry and Developmental Biology
University of Helsinki, Department of Biochemistry and Developmental Biology
University of Helsinki, Department of Biochemistry and Developmental Biology
University of Helsinki, Department of Biochemistry and Developmental Biology
University of Helsinki, Department of Biochemistry and Developmental Biology
Date: 2019-04-18
Language: eng
Number of pages: 24
Belongs to series: Molecular Cell
ISSN: 1097-2765
URI: http://hdl.handle.net/10138/307755
Abstract: DNA damage response (DDR) involves dramatic transcriptional alterations, the mechanisms of which remain ill defined. Here, we show that following genotoxic stress, the RNA-binding motif protein 7 (RBM7) stimulates RNA polymerase II (Pol II) transcription and promotes cell viability by activating the positive transcription elongation factor b (P-TEFb) via its release from the inhibitory 7SK small nuclear ribonucleoprotein (7SK snRNP). This is mediated by activation of p38MAPK, which triggers enhanced binding of RBM7 with core subunits of 7SK snRNP. In turn, P-TEFb relocates to chromatin to induce transcription of short units, including key DDR genes and multiple classes of non-coding RNAs. Critically, interfering with the axis of RBM7 and P-TEFb provokes cellular hypersensitivity to DNA-damage-inducing agents due to activation of apoptosis. Our work uncovers the importance of stress-dependent stimulation of Pol II pause release, which enables a pro-survival transcriptional response that is crucial for cell fate upon genotoxic insult.
Subject: 7SK SNRNP
DNA-DAMAGE
ELONGATION
EXOSOME TARGETING COMPLEX
GENE-EXPRESSION
INHIBITION
NONCODING RNA
REPAIR
RNA-POLYMERASE-II
ULTRAVIOLET-LIGHT
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
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