PPM1G Binds 7SK RNA and Hexim1 To Block P-TEFb Assembly into the 7SK snRNP and Sustain Transcription Elongation
| Autor: | Swapna Aravind Gudipaty, Emily L. Morton, Ryan P. McNamara, Iván D'Orso |
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| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Transcriptional Activation RNA polymerase II Ataxia Telangiectasia Mutated Proteins Transcription (biology) RNA Small Nuclear 7SK RNA Phosphoprotein Phosphatases Humans Positive Transcriptional Elongation Factor B snRNP P-TEFb Molecular Biology Ribonucleoprotein General transcription factor biology NF-kappa B RNA-Binding Proteins Articles Cell Biology Ribonucleoproteins Small Nuclear Molecular biology Protein Structure Tertiary Cell biology Protein Phosphatase 2C HEK293 Cells biology.protein Nucleic Acid Conformation RNA Polymerase II Transcription factor II D DNA Damage HeLa Cells Protein Binding Transcription Factors |
| Zdroj: | Molecular and Cellular Biology. 35:3810-3828 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.00226-15 |
| Popis: | Transcription elongation programs are vital for the precise regulation of several biological processes. One key regulator of such programs is the P-TEFb kinase, which phosphorylates RNA polymerase II (Pol II) once released from the inhibitory 7SK small nuclear ribonucleoprotein (snRNP) complex. Although mechanisms of P-TEFb release from the snRNP are becoming clearer, how P-TEFb remains in the 7SK-unbound state to sustain transcription elongation programs remains unknown. Here we report that the PPM1G phosphatase (inducibly recruited by nuclear factor κB [NF-κB] to target promoters) directly binds 7SK RNA and the kinase inhibitor Hexim1 once P-TEFb has been released from the 7SK snRNP. This dual binding activity of PPM1G blocks P-TEFb reassembly onto the snRNP to sustain NF-κB-mediated Pol II transcription in response to DNA damage. Notably, the PPM1G-7SK RNA interaction is direct, kinetically follows the recruitment of PPM1G to promoters to activate NF-κB transcription, and is reversible, since the complex disassembles before resolution of the program. Strikingly, we found that the ataxia telangiectasia mutated (ATM) kinase regulates the interaction between PPM1G and the 7SK snRNP through site-specific PPM1G phosphorylation. The precise and temporally regulated interaction of a cellular enzyme and a noncoding RNA provides a new paradigm for simultaneously controlling the activation and maintenance of inducible transcription elongation programs. |
| Databáze: | OpenAIRE |
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