@Article{Bugai2019, author = {Bugai, Andrii and Quaresma, Alexandre J C and Friedel, Caroline C. and Lenasi, Tina and Düster, Robert and Sibley, Christopher R and Fujinaga, Koh and Kukanja, Petra and Hennig, Thomas and Blasius, Melanie and Geyer, Matthias and Ule, Jernej and Dölken, Lars and Barborič, Matjaž}, title = {P-TEFb Activation by RBM7 Shapes a Pro-survival Transcriptional Response to Genotoxic Stress}, journal = {Molecular cell}, year = {2019}, month = feb, issn = {1097-4164}, __markedentry = {[friedel:6]}, 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 p38 , 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.}, country = {United States}, doi = {10.1016/j.molcel.2019.01.033}, issn-linking = {1097-2765}, keywords = {7SK snRNP; CDK9; DNA damage response; P-TEFb; Pol II elongation; Pol II pause release; RBM7; apoptosis; genotoxic stress; p38 MAP kinase}, nlm-id = {9802571}, owner = {NLM}, pii = {S1097-2765(19)30053-X}, pmid = {30824372}, pubmodel = {Print-Electronic}, pubstatus = {aheadofprint}, revised = {2019-03-02}, volume = {74}, number = {2}, pages = {254-267} }