ArticleMolecular and cellular biology2012
Transition step during assembly of HIV Tat:P-TEFb transcription complexes and transfer to TAR RNA.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 58 citations in OpenAlex.
- Thermodynamic prediction of RNA cellular activity from sequence via conformational ensembles.Cell · 2026Article
- HEXIM1 inter-monomer autoinhibition governs 7SK RNA binding specificity and P-TEFb inactivation.Nature communications · 2026Article
- Single-molecule live imaging of subunit interactions and exchange within cellular regulatory complexes.Molecular cell · 2025Article
- FUBP3 enhances HIV-1 transcriptional activity and regulates immune response pathways in T cells.Molecular therapy. Nucleic acids · 2025Article
- The HIV-1 Transcriptional Program: From Initiation to Elongation Control.Journal of molecular biology · 2025Review
- The cell biology of HIV-1 latency and rebound.Retrovirology · 2024Review
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- Enhanced NF-κB activation via HIV-1 Tat-TRAF6 cross-talk.Science advances · 2024Article
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- HnRNP A1/A2 Proteins Assemble onto 7SK snRNA via Context Dependent Interactions.Journal of molecular biology · 2021Article
- Co-crystal structures of HIV TAR RNA bound to lab-evolved proteins show key roles for arginine relevant to the design of cyclic peptide TAR inhibitors.The Journal of biological chemistry · 2020Article
- HIV-1 Proviral Transcription and Latency in the New Era.Viruses · 2020Review
- From Entry to Egress: Strategic Exploitation of the Cellular Processes by HIV-1.Frontiers in microbiology · 2020Review
- Face-time with TAR: Portraits of an HIV-1 RNA with diverse modes of effector recognition relevant for drug discovery.The Journal of biological chemistry · 2019Review
- Transcriptional Circuit Fragility Influences HIV Proviral Fate.Cell reports · 2019Article
- Genetic variation and function of the HIV-1 Tat protein.Medical microbiology and immunology · 2019Review
- Article
- HIV-1 Tat interactions with cellular 7SK and viral TAR RNAs identifies dual structural mimicry.Nature communications · 2018Article
- The HIV-1 Tat Protein Enhances Splicing at the Major Splice Donor Site.Journal of virology · 2018Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Transcription factors regulate eukaryotic RNA polymerase II (Pol II) activity by assembling and remodeling complexes at multiple steps in the transcription cycle. In HIV, we previously proposed a two-step model where the viral Tat protein first preassembles at the promoter with an inactive P-TEFb:7SK snRNP complex and later transfers P-TEFb to TAR on the nascent transcript, displacing the inhibitory snRNP and resulting in Pol II phosphorylation and stimulation of elongation. It is unknown how the Tat:P-TEFb complex transitions to TAR to activate the P-TEFb kinase. Here, we show that P-TEFb artificially recruited to the nascent transcript is not competent for transcription but rather remains inactive due to its assembly with the 7SK snRNP. Tat supplied in trans is able to displace the kinase inhibitor Hexim1 from the snRNP and activate P-TEFb, thereby uncoupling Tat requirements for kinase activation and TAR binding. By combining comprehensive mutagenesis of Tat with multiple cell-based reporter assays that probe the activity of Tat in different arrangements, we genetically defined a transition step in which preassembled Tat:P-TEFb complexes switch to TAR. We propose that a conserved network of residues in Tat has evolved to control this transition and thereby switch the host elongation machinery to viral transcription.
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