Evidence map›Paper›PMID 36920904›Full record

ArticleCell reports2023

A combinatorial approach to uncover an additional Integrator subunit.

Sarah R Offley, Moritz M Pfleiderer, Avery Zucco, Angelique Fraudeau, Sarah A Welsh, Michal Razew, Wojciech P Galej, Alessandro Gardini

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

23 citing papers in PubMed, 34 citations in OpenAlex.

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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

8 authors at 2 institutions in 2 countries.

Sarah R OffleyThe Wistar Institute, Philadelphia, PA 19103, USA; Cell and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Moritz M PfleidererEuropean Molecular Biology Laboratory, 71 Avenue des Martyrs, 38042 Grenoble, France.
Avery ZuccoThe Wistar Institute, Philadelphia, PA 19103, USA.
Angelique FraudeauEuropean Molecular Biology Laboratory, 71 Avenue des Martyrs, 38042 Grenoble, France.
Sarah A WelshThe Wistar Institute, Philadelphia, PA 19103, USA.
Michal RazewEuropean Molecular Biology Laboratory, 71 Avenue des Martyrs, 38042 Grenoble, France.
Wojciech P GalejEuropean Molecular Biology Laboratory, 71 Avenue des Martyrs, 38042 Grenoble, France. Electronic address: wgalej@embl.fr.
Alessandro GardiniThe Wistar Institute, Philadelphia, PA 19103, USA. Electronic address: agardini@wistar.org.
European Molecular Biology Laboratory · FRThe Wistar Institute · US

Funding

Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Luis J Montaner · 1985 to 2026
$75.9M
TRAINING PROGRAM IN BASIC CANCER RESEARCHT32CA009171 · NCI · WISTAR INSTITUTE · PI Alessandro Gardini · 1985 to 2026
$15.3M
Role of an Integrator-EGR axis in the regulation of myeloid enhancers (Admin Supp)R01HL141326 · NHLBI · WISTAR INSTITUTE · PI GARDINI, ALESSANDRO · 2019 to 2023
$2.7M
NCI NIH HHS P30 CA010815NCI NIH HHS T32 CA009171NHLBI NIH HHS R01 HL141326
6 · The paper itself

Abstract

RNA polymerase II (RNAPII) controls expression of all protein-coding genes and most noncoding loci in higher eukaryotes. Calibrating RNAPII activity requires an assortment of polymerase-associated factors that are recruited at sites of active transcription. The Integrator complex is one of the most elusive transcriptional regulators in metazoans, deemed to be recruited after initiation to help establish and modulate paused RNAPII. Integrator is known to be composed of 14 subunits that assemble and operate in a modular fashion. We employed proteomics and machine-learning structure prediction (AlphaFold2) to identify an additional Integrator subunit, INTS15. We report that INTS15 assembles primarily with the INTS13/14/10 module and interfaces with the Int-PP2A module. Functional genomics analysis further reveals a role for INTS15 in modulating RNAPII pausing at a subset of genes. Our study shows that omics approaches combined with AlphaFold2-based predictions provide additional insights into the molecular architecture of large and dynamic multiprotein complexes.

Indexed as

RNA Polymerase IITranscription, GeneticRNA Polymerase IIAlphaFold2CP: NeuroscienceIntegrator complexlarge protein complexesmolecular modelingomicspause-releaseRNA polymerase IIRNA polymerase II pausingtranscriptiontranscriptional regulationtranscription factors

Identifiers

PMID36920904
PMCPMC10312363
OpenAlexW4324145210

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.