Evidence map›Paper›PMID 38955181›Full record

ArticleMolecular cell2024

An IDR-dependent mechanism for nuclear receptor control of Mediator interaction with RNA polymerase II.

Haiyan Zhao, Jiaqin Li, Yufei Xiang, Sohail Malik, Supriya V Vartak, Giovana M B Veronezi, Natalie Young, McKayla Riney, Jens Kalchschmidt, Andrea Conte and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Review
  2. Article
  3. The molecular basis of transcription initiation by RNA polymerase II.Nature reviews. Molecular cell biology · 2026
    Review
  4. Article
  5. Current Challenges of Transcription Compartmentalization Research.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  6. Review
  7. The Polymers of Life: Exploring Cellular Function Through Polymer Concepts.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  8. Review
  9. Article
  10. Article
  11. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Haiyan ZhaoDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical School, Aurora, CO 80045, USA.
Jiaqin LiDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical School, Aurora, CO 80045, USA.
Yufei XiangCenter of Protein Engineering and Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Sohail MalikLaboratory of Biochemistry and Molecular Biology, Rockefeller University, New York, NY 10065, USA.
Supriya V VartakLymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
Giovana M B VeroneziDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical School, Aurora, CO 80045, USA.
Natalie YoungDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical School, Aurora, CO 80045, USA.
McKayla RineyDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical School, Aurora, CO 80045, USA.
Jens KalchschmidtLymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
Andrea ConteLymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
Seol Kyoung JungBiodata Mining and Discovery Section, NIAMS, NIH, Bethesda, MD 20892, USA.
Srinivas RamachandranDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical School, Aurora, CO 80045, USA; RNA Bioscience Initiative, University of Colorado Anschutz Medical School, Aurora, CO 80045, USA.
Robert G RoederLaboratory of Biochemistry and Molecular Biology, Rockefeller University, New York, NY 10065, USA.
Yi ShiCenter of Protein Engineering and Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Rafael CasellasLymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
Francisco J AsturiasDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical School, Aurora, CO 80045, USA. Electronic address: francisco.asturias@cuanschutz.edu.

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
RAG and AID biologyZIAAR041148 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI O'SHEA, JOHN · 2009 to 2025
$44.8M
STRUCTURAL STUDIES OF EUKARYOTIC TRANSCRIPTIONR01GM067167 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI ASTURIAS, FRANCISCO J · 2003 to 2025
$9.2M
Transgenic and Gene Targeting CoreP30AR057212 · NIAMS · UNIVERSITY OF COLORADO DENVER · PI HOGAN, CHRISTOPHER J · 2009 to 2018
$6.2M
Molecular mechanisms of estrogen receptor-dependent transcription regulationR01CA234575 · NCI · ROCKEFELLER UNIVERSITY · PI ROEDER, ROBERT G · 2019 to 2023
$3.1M
Mapping the Dynamic Interactome of Ig-fold Membrane Proteins Using Nanobody-Based ToolsR35GM137905 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Yi Shi · 2020 to 2026
$2.8M
Maintenance of cellular memory through replicationR35GM133434 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI RAMACHANDRAN, SRINIVAS · 2019 to 2023
$2.0M
Mechanistic studies of transcription initiation and elongation functions of an RNA polymerase II variant, Pol II(G), that is implicated in development and cancerR01CA273709 · NCI · ROCKEFELLER UNIVERSITY · PI ROBERT G ROEDER · 2022 to 2026
$1.9M
Talos Arctica Electron Microscope Imaging System UpgradeS10OD036446 · OD · UNIVERSITY OF COLORADO DENVER · PI ASTURIAS, FRANCISCO J · 2024 to 2024
$1.4M
NCI NIH HHS P30 CA046934NCI NIH HHS R01 CA234575NCI NIH HHS R01 CA273709NIAMS NIH HHS P30 AR057212NIGMS NIH HHS R01 GM067167NIGMS NIH HHS R35 GM133434NIGMS NIH HHS R35 GM137905NIH HHS S10 OD036446
6 · The paper itself

Abstract

The essential Mediator (MED) coactivator complex plays a well-understood role in regulation of basal transcription in all eukaryotes, but the mechanism underlying its role in activator-dependent transcription remains unknown. We investigated modulation of metazoan MED interaction with RNA polymerase II (RNA Pol II) by antagonistic effects of the MED26 subunit and the CDK8 kinase module (CKM). Biochemical analysis of CKM-MED showed that the CKM blocks binding of the RNA Pol II carboxy-terminal domain (CTD), preventing RNA Pol II interaction. This restriction is eliminated by nuclear receptor (NR) binding to CKM-MED, which enables CTD binding in a MED26-dependent manner. Cryoelectron microscopy (cryo-EM) and crosslinking-mass spectrometry (XL-MS) revealed that the structural basis for modulation of CTD interaction with MED relates to a large intrinsically disordered region (IDR) in CKM subunit MED13 that blocks MED26 and CTD interaction with MED but is repositioned upon NR binding. Hence, NRs can control transcription initiation by priming CKM-MED for MED26-dependent RNA Pol II interaction.

Indexed as

Cryoelectron MicroscopyCyclin-Dependent Kinase 8Mediator ComplexProtein BindingRNA Polymerase IIAnimalsBinding SitesHEK293 CellsHumansIntrinsically Disordered ProteinsProtein Interaction Domains and MotifsReceptors, Cytoplasmic and NuclearCDK8 protein, humanCyclin-Dependent Kinase 8Intrinsically Disordered ProteinsMED13 protein, humanMediator ComplexReceptors, Cytoplasmic and NuclearRNA Polymerase IIactivationCDK8 kinase moduleeukaryotic transcriptionMED26Mediator complexnuclear receptorsRNA polymerase II CTDtranscription regulation

Identifiers

PMID38955181
PMCPMC11283359

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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.