ArticlePloS one2010
The mechanism of release of P-TEFb and HEXIM1 from the 7SK snRNP by viral and cellular activators includes a conformational change in 7SK.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 112 citations in OpenAlex.
- Phosphorylation of CDK9 at Ser175 enhances HIV transcription and is a marker of activated P-TEFb in CD4(+) T lymphocytes.PLoS pathogens · 2013Trial
- BRD proteins in human retroviral infection: emerging evidence from HIV-1 and future perspectives for HTLV-1.Molecular biology reports · 2026Review
- Structural basis for P-TEFb association with BRD4.bioRxiv : the preprint server for biology · 2026Article
- Multi-site DMS probing reveals higher-order structure of RNA-protein complexes in living cells.Molecular cell · 2026Article
- Block-and-Lock Approaches for HIV Cure: Mechanistic Insights, Challenges, and Emerging Role of CPSF6.International journal of molecular sciences · 2026Review
- Solution structure determination and biophysical characterization studies of 7SK RNP and 7SL SRP RNAs.RNA (New York, N.Y.) · 2025Article
- Chemical Probe Discovery for DEAD-Box RNA-Binding Protein DDX21 Using Small-Molecule Microarrays.ACS chemical biology · 2025Article
- Single-molecule live imaging of subunit interactions and exchange within cellular regulatory complexes.Molecular cell · 2025Article
- BRD4 modulator ZL0580 and LEDGINs additively block and lock HIV-1 transcription.Nature communications · 2025Article
- BET degraders reveal BRD4 disruption of 7SK and P-TEFb is critical for effective reactivation of latent HIV in CD4+ T-cells.Journal of virology · 2025Article
- The HIV-1 Transcriptional Program: From Initiation to Elongation Control.Journal of molecular biology · 2025Review
- IKAROS: from chromatin organization to transcriptional elongation control.Cell death and differentiation · 2025Review
- Visualizing RNA structure ensembles by single-molecule correlated chemical probing.Current opinion in structural biology · 2024Review
- Release of P-TEFb from the Super Elongation Complex promotes HIV-1 latency reversal.PLoS pathogens · 2024Article
- Release of P-TEFb from the Super Elongation Complex promotes HIV-1 latency reversal.bioRxiv : the preprint server for biology · 2024Article
- Review
- Catalytic activity of the Bin3/MePCE methyltransferase domain is dispensable for 7SK snRNP function in Drosophila melanogaster.Genetics · 2024Article
- NMolecular cell · 2023Article
- The NELF pausing checkpoint mediates the functional divergence of Cdk9.Nature communications · 2023Article
- Progress in 7SK ribonucleoprotein structural biology.Frontiers in molecular biosciences · 2023Review
27 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe positive transcription elongation factor, P-TEFb, is required for the production of mRNAs, however the majority of the factor is present in the 7SK snRNP where it is inactivated by HEXIM1. Expression of HIV-1 Tat leads to release of P-TEFb and HEXIM1 from the 7SK snRNP in vivo, but the release mechanisms are unclear. METHODOLOGY/PRINCIPAL
findingsWe developed an in vitro P-TEFb release assay in which the 7SK snRNP immunoprecipitated from HeLa cell lysates using antibodies to LARP7 was incubated with potential release factors. We found that P-TEFb was directly released from the 7SK snRNP by HIV-1 Tat or the P-TEFb binding region of the cellular activator Brd4. Glycerol gradient sedimentation analysis was used to demonstrate that the same Brd4 protein transfected into HeLa cells caused the release of P-TEFb and HEXIM1 from the 7SK snRNP in vivo. Although HEXIM1 binds tightly to 7SK RNA in vitro, release of P-TEFb from the 7SK snRNP is accompanied by the loss of HEXIM1. Using a chemical modification method, we determined that concomitant with the release of HEXIM1, 7SK underwent a major conformational change that blocks re-association of HEXIM1. CONCLUSIONS/SIGNIFICANCE: Given that promoter proximally paused polymerases are present on most human genes, understanding how activators recruit P-TEFb to those genes is critical. Our findings reveal that the two tested activators can extract P-TEFb from the 7SK snRNP. Importantly, we found that after P-TEFb is extracted a dramatic conformational change occurred in 7SK concomitant with the ejection of HEXIM1. Based on our findings, we hypothesize that reincorporation of HEXIM1 into the 7SK snRNP is likely the regulated step of reassembly of the 7SK snRNP containing P-TEFb.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.