P-TEFb Activation by RBM7 Shapes a Pro-survival Transcriptional Response to Genotoxic Stress
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
P-TEFb Activation by RBM7 Shapes a Pro-survival Transcriptional Response to Genotoxic Stress. / Bugai, Andrii; Quaresma, Alexandre J.C.; Friedel, Caroline C.; Lenasi, Tina; Düster, Robert; Sibley, Christopher R.; Fujinaga, Koh; Kukanja, Petra; Hennig, Thomas; Blasius, Melanie; Geyer, Matthias; Ule, Jernej; Dölken, Lars; Barborič, Matjaž.
In: Molecular Cell, Vol. 74, No. 2, 2019, p. 254-267.e10.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - P-TEFb Activation by RBM7 Shapes a Pro-survival Transcriptional Response to Genotoxic Stress
AU - Bugai, Andrii
AU - Quaresma, Alexandre J.C.
AU - Friedel, Caroline C.
AU - Lenasi, Tina
AU - Düster, Robert
AU - Sibley, Christopher R.
AU - Fujinaga, Koh
AU - Kukanja, Petra
AU - Hennig, Thomas
AU - Blasius, Melanie
AU - Geyer, Matthias
AU - Ule, Jernej
AU - Dölken, Lars
AU - Barborič, Matjaž
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - 7SK snRNP
KW - apoptosis
KW - CDK9
KW - DNA damage response
KW - genotoxic stress
KW - P-TEFb
KW - p38 MAP kinase
KW - Pol II elongation
KW - Pol II pause release
KW - RBM7
U2 - 10.1016/j.molcel.2019.01.033
DO - 10.1016/j.molcel.2019.01.033
M3 - Journal article
C2 - 30824372
AN - SCOPUS:85064186193
VL - 74
SP - 254-267.e10
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 2
ER -
ID: 216865015