Evidence map›Paper›PMID 41540012›Full record

ArticleNature communications2026

HEXIM1 inter-monomer autoinhibition governs 7SK RNA binding specificity and P-TEFb inactivation.

Yuan Yang, Maria Grazia Murrali, Sabrina Galvan, Yaqiang Wang, Christine Stephen, Neha Ajjampore, Xiaoyu Wang, Juli Feigon

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Yuan YangDepartment of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA, USA. yuanyangwhu@ucla.edu.ORCID http://orcid.org/0000-0002-9538-6369
Maria Grazia MurraliDepartment of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA, USA.
Sabrina GalvanDepartment of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA, USA.
Yaqiang WangDepartment of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-6822-4778
Christine StephenDepartment of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA, USA.
Neha AjjamporeDepartment of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA, USA.
Xiaoyu WangDepartment of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA, USA.
Juli FeigonDepartment of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA, USA. feigon@mbi.ucla.edu.ORCID http://orcid.org/0000-0003-3376-435X

Funding

Structural biology of telomerase and telomeresR35GM131901 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JULI FEIGON · 2019 to 2026
$5.7M
Structural biology of 7SK RNP and its interaction with HIV-1 TatR01AI155170 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JULI FEIGON · 2020 to 2026
$4.8M
800 MHz NMR Console and Cryoprobe ReplacementS10OD025073 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FEIGON, JULI · 2018 to 2018
$1.1M
Bruker Avance III Console and QCI Cryoprobe for a 600 MHz NMR SpectrometerS10OD016336 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CLUBB, ROBERT THOMPSON · 2014 to 2014
$600k
NIAID NIH HHS R01 AI155170NIGMS NIH HHS R35 GM131901NIH HHS S10 OD016336NIH HHS S10 OD025073U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R01AI155170U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM131901
6 · The paper itself

Abstract

Hexim proteins are key RNA-dependent regulators of eukaryotic transcription through 7SK-dependent sequestration and inactivation of the kinase P-TEFb (Cdk9-CyclinT1/2) in the 7SK RNP. P-TEFb activity drives release of RNA polymerase II from promoter-proximal pausing for eukaryotic and HIV-1 transcription. The molecular mechanism by which 7SK binding overcomes an intrinsic Hexim autoinhibition for subsequent P-TEFb inactivation has remained unresolved. Here, using NMR and biophysical methods we demonstrate that Hexim1 homodimer engages two high-affinity sites on 7SK RNA. This dual-site binding triggers a conformational rearrangement in Hexim1's disordered central region that unmasks the Cdk9-binding site, which is otherwise sequestered within an inter-monomer dimer interface. These findings reveal how Hexim autoinhibition dictates its specificity for 7SK RNA and prevents premature P-TEFb inhibition in the absence of 7SK, thereby providing a mechanistic understanding of Hexim/P-TEFb assembly into the 7SK RNP and further considerations for understanding Hexim-Tat competition during viral transcription.

Indexed as

Positive Transcriptional Elongation Factor BRNA-Binding ProteinsRNA, Small CytoplasmicBinding SitesCyclin-Dependent Kinase 9Cyclin THIV-1HumansModels, MolecularProtein BindingRNA, Long NoncodingTranscription FactorsTranscription, GeneticCCNT1 protein, humanCDK9 protein, humanCyclin-Dependent Kinase 9Cyclin THEXIM1 protein, humanlong non-coding RNA 7SK, humanPositive Transcriptional Elongation Factor BRNA-Binding ProteinsRNA, Long NoncodingRNA, Small CytoplasmicTranscription Factors

Identifiers

PMID41540012
PMCPMC12901311

What Socratic 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 Socratic graph.