Evidence map›Paper›PMID 23007159›Full record

ArticleMolecular and cellular biology2012

Transition step during assembly of HIV Tat:P-TEFb transcription complexes and transfer to TAR RNA.

Iván D'Orso, Gwendolyn M Jang, Alexander W Pastuszak, Tyler B Faust, Elizabeth Quezada, David S Booth, Alan D Frankel

Open access · bronzeAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
1.9field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 58 citations in OpenAlex.

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  17. Genetic variation and function of the HIV-1 Tat protein.Medical microbiology and immunology · 2019
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Iván D'OrsoDepartment of Biochemistry and Biophysics, University of California, San Francisco, California, USA. ivan.dorso@utsouthwestern.edu
Gwendolyn M Jang
Alexander W Pastuszak
Tyler B Faust
Elizabeth Quezada
David S Booth
Alan D Frankel
University of California, San Francisco · US

Funding

X-ray Screening and Rapid Structure DeterminationP50GM082250 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FRANKEL, ALAN D · 2007 to 2018
$48.8M
Maximizing Opportunities for Research Excellence - Evaluation Training SupplementR25GM056847 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DUNCAN, D'ANNE S., SELLO, JASON K · 1998 to 2023
$14.1M
PREDOCTORAL TRAINING IN DEVELOPMENTAL BIOLOGYT32HD007470 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Todd Nystul · 1994 to 2026
$7.7M
ACTIVITY AND INHIBITION OF THE TAT PROTEIN FROM HIVR01AI029135 · NIAID · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI FRANKEL, ALAN D · 1989 to 2010
$2.8M
Assembly of HIV -1 and Cellular Transcription Elongation ComplexesR00AI083087 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI D'ORSO, IVAN · 2011 to 2012
$514k
Structural requirements for the nuclear export of HIV RNAF31GM095350 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BOOTH, DAVID SCOTT · 2011 to 2013
$99k
Splice site recognition and protein assemblyF32GM077868 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JANG, GWENDOLYN M · 2007 to 2009
$97k
Assembly of HIV -1 and Cellular Transcription Elongation ComplexesK99AI083087 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI D'ORSO, IVAN · 2009 to 2009
$90k
NIAID NIH HHS AI29135NIAID NIH HHS K99 AI083087NIAID NIH HHS R00 AI083087NIAID NIH HHS R00AI083087NIAID NIH HHS R01 AI029135NICHD NIH HHS T32 HD007470NIGMS NIH HHS F31GM09535NIGMS NIH HHS F31 GM095350NIGMS NIH HHS F32 GM077868NIGMS NIH HHS GM077868NIGMS NIH HHS P50 GM082250NIGMS NIH HHS R25 GM056847NIGMS NIH HHS R25GM56847PHS HHS K99A112185
6 · The paper itself

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.

Indexed as

Gene Expression Regulation, ViralHIV Long Terminal RepeatAmino Acid SequenceCell LineConserved SequenceHIVHIV InfectionsHumansModels, MolecularMolecular Sequence DataMutationPositive Transcriptional Elongation Factor BRibonucleoproteins, Small NuclearRNA-Binding ProteinsRNA, Viraltat Gene Products, Human Immunodeficiency VirusHEXIM1 protein, humanPositive Transcriptional Elongation Factor BRibonucleoproteins, Small NuclearRNA-Binding ProteinsRNA, Viraltat Gene Products, Human Immunodeficiency VirusTranscription Factors

Identifiers

PMID23007159
PMCPMC3497596
OpenAlexW2120231504

What OpenQuestion holds

Textmetadata
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Registered trials

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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.