TY  - JOUR
A1  - Bugai, Andrii
A1  - Quaresma, Alexandre J. C.
A1  - Friedel, Caroline C.
A1  - Lenasi, Tina
A1  - Düster, Robert
A1  - Sibley, Christopher R.
A1  - Fujinaga, Koh
A1  - Kukanja, Petra
A1  - Hennig, Thomas
A1  - Blasius, Melanie
A1  - Geyer, Matthias
A1  - Ule, Jernej
A1  - Dölken, Lars
A1  - Barborič, Matjaž
T1  - P-TEFb Activation by RBM7 Shapes a Pro-survival Transcriptional Response to Genotoxic Stress
JF  - Molecular Cell
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.
KW  - Pol II elongation
KW  - Pol II pause release
KW  - P-TEFb
KW  - CDK9
KW  - 7SK snRNP
KW  - RBM7
KW  - genotoxic stress
KW  - DNA damage response
KW  - p38 MAP kinase
KW  - apoptosis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221726
VL  - 74
ER  - 
TY  - JOUR
A1  - Baluapuri, Apoorva
A1  - Hofstetter, Julia
A1  - Dudvarski Stankovic, Nevenka
A1  - Endres, Theresa
A1  - Bhandare, Pranjali
A1  - Vos, Seychelle Monique
A1  - Adhikari, Bikash
A1  - Schwarz, Jessica Denise
A1  - Narain, Ashwin
A1  - Vogt, Markus
A1  - Wang, Shuang-Yan
A1  - Düster, Robert
A1  - Jung, Lisa Anna
A1  - Vanselow, Jens Thorsten
A1  - Wiegering, Armin
A1  - Geyer, Matthias
A1  - Maric, Hans Michael
A1  - Gallant, Peter
A1  - Walz, Susanne
A1  - Schlosser, Andreas
A1  - Cramer, Patrick
A1  - Eilers, Martin
A1  - Wolf, Elmar
T1  - MYC Recruits SPT5 to RNA Polymerase II to Promote Processive Transcription Elongation
JF  - Molecular Cell
N2  - The MYC oncoprotein binds to promoter-proximal regions of virtually all transcribed genes and enhances RNA polymerase II (Pol II) function, but its precise mode of action is poorly understood. Using mass spectrometry of both MYC and Pol II complexes, we show here that MYC controls the assembly of Pol II with a small set of transcription elongation factors that includes SPT5, a subunit of the elongation factor DSIF. MYC directly binds SPT5, recruits SPT5 to promoters, and enables the CDK7-dependent transfer of SPT5 onto Pol II. Consistent with known functions of SPT5, MYC is required for fast and processive transcription elongation. Intriguingly, the high levels of MYC that are expressed in tumors sequester SPT5 into non-functional complexes, thereby decreasing the expression of growth-suppressive genes. Altogether, these results argue that MYC controls the productive assembly of processive Pol II elongation complexes and provide insight into how oncogenic levels of MYC permit uncontrolled cellular growth.
KW  - MYC
KW  - SPT5
KW  - SUPT5H
KW  - SPT6
KW  - RNA polymerase II
KW  - transcription
KW  - elongation rate
KW  - processivity
KW  - directionality
KW  - tumorigenesis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221438
VL  - 74
ER  -