Evidence map›Paper›PMID 29845934›Full record

ArticleeLife2018

The HIV-1 Tat protein recruits a ubiquitin ligase to reorganize the 7SK snRNP for transcriptional activation.

Tyler B Faust, Yang Li, Curtis W Bacon, Gwendolyn M Jang, Amit Weiss, Bhargavi Jayaraman, Billy W Newton, Nevan J Krogan, Iván D'Orso, Alan D Frankel

Open access · goldAbstract read
In one paragraph

Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

27 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. OverexpressionViruses · 2022
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. CDK9 keeps RNA polymerase II on track.Cellular and molecular life sciences : CMLS · 2021
    Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. Specificity in Ubiquitination Triggered by Virus Infection.International journal of molecular sciences · 2020
    Review
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

10 authors at 3 institutions in 1 country.

Tyler B FaustDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
Yang LiDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.ORCID 0000-0003-0216-0350
Curtis W BaconDepartment of Microbiology, University of Texas Southwestern Medical Center, Dallas, United States.ORCID 0000-0001-6454-5470
Gwendolyn M JangDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States.
Amit WeissDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
Bhargavi JayaramanDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
Billy W NewtonDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States.
Nevan J KroganDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States.
Iván D'OrsoDepartment of Microbiology, University of Texas Southwestern Medical Center, Dallas, United States.ORCID 0000-0002-1409-2351
Alan D FrankelDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.ORCID 0000-0002-2525-9508
University of California, San Francisco · USGladstone Institutes · USThe University of Texas Southwestern Medical Center · US

Funding

Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS · 1988 to 2026
$93.6M
X-ray Screening and Rapid Structure DeterminationP50GM082250 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FRANKEL, ALAN D · 2007 to 2018
$48.8M
Transcriptional regulatory mechanisms shaping HIV proviral fateR01AI114362 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI D'ORSO, IVAN · 2015 to 2024
$4.6M
Transcriptional regulatory mechanisms shaping HIV proviral fateR37AI114362 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI Ivan D'Orso · 2025 to 2026
$1.0M
NIAID NIH HHS P30 AI027763NIAID NIH HHS R01 AI114362NIAID NIH HHS R01AI114362NIAID NIH HHS R37 AI114362NIAID NIH HHS RO1AI114362NIGMS NIH HHS P50 GM082250NIGMS NIH HHS P50GM082250
6 · The paper itself

Abstract

The HIV-1 Tat protein hijacks P-TEFb kinase to activate paused RNA polymerase II (RNAP II) at the viral promoter. Tat binds additional host factors, but it is unclear how they regulate RNAP II elongation. Here, we identify the cytoplasmic ubiquitin ligase UBE2O as critical for Tat transcriptional activity. Tat hijacks UBE2O to ubiquitinate the P-TEFb kinase inhibitor HEXIM1 of the 7SK snRNP, a fraction of which also resides in the cytoplasm bound to P-TEFb. HEXIM1 ubiquitination sequesters it in the cytoplasm and releases P-TEFb from the inhibitory 7SK complex. Free P-TEFb then becomes enriched in chromatin, a process that is also stimulated by treating cells with a CDK9 inhibitor. Finally, we demonstrate that UBE2O is critical for P-TEFb recruitment to the HIV-1 promoter. Together, the data support a unique model of elongation control where non-degradative ubiquitination of nuclear and cytoplasmic 7SK snRNP pools increases P-TEFb levels for transcriptional activation.

Indexed as

Active Transport, Cell NucleusAmino Acid SequenceCell NucleusChromatinDichlororibofuranosylbenzimidazoleHEK293 CellsHeLa CellsHIV-1HumansModels, BiologicalNuclear Localization SignalsPositive Transcriptional Elongation Factor BProtein BindingProtein TransportRibonucleoproteins, Small NuclearRNA-Binding ProteinsChromatinDichlororibofuranosylbenzimidazoleHEXIM1 protein, humanNuclear Localization SignalsPositive Transcriptional Elongation Factor BRibonucleoproteins, Small NuclearRNA-Binding Proteinstat Gene Products, Human Immunodeficiency VirusTranscription FactorsUBE2O protein, humanUbiquitin-Conjugating Enzymes7SK snRNPbiochemistrychemical biologyHIV-1host-pathogen interactionshumannon-degradative ubiquitinationnuclear importtranscription elongation

Identifiers

PMID29845934
PMCPMC5999396
OpenAlexW2806503704

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.