Evidence map›Paper›PMID 33400923›Full record

ArticleMolecular cell2021

Hyperosmotic stress alters the RNA polymerase II interactome and induces readthrough transcription despite widespread transcriptional repression.

Nicolle A Rosa-Mercado, Joshua T Zimmer, Maria Apostolidi, Jesse Rinehart, Matthew D Simon, Joan A Steitz

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
6.7field-weighted citation impact, top 2% 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

69 citing papers in PubMed, 103 citations in OpenAlex.

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9 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 1 country.

Nicolle A Rosa-MercadoDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06536, USA.
Joshua T ZimmerDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06536, USA.
Maria ApostolidiDepartment of Cellular and Molecular Physiology, Yale University, New Haven, CT 06510, USA; Systems Biology Institute, Yale University, West Haven, CT 06477, USA.
Jesse RinehartDepartment of Cellular and Molecular Physiology, Yale University, New Haven, CT 06510, USA; Systems Biology Institute, Yale University, West Haven, CT 06477, USA.
Matthew D SimonDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06536, USA.
Joan A SteitzDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06536, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT 06536, USA. Electronic address: joan.steitz@yale.edu.
Yale University · USHoward Hughes Medical Institute · US

Funding

The second phase of NIH Common Fund 4D Nucleome Network Organizational HubU01CA200147 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ZHONG, SHENG · 2015 to 2024
$22.0M
Predoctoral Training Program in VirologyT32AI055403 · NIAID · YALE UNIVERSITY · PI KUMAR, PRITI, MOTHES, WALTHER H · 2003 to 2024
$3.6M
Revealing the dynamics of RNA metabolism with nucleotide recoding chemistryR01GM137117 · NIGMS · YALE UNIVERSITY · PI Matthew David Simon · 2020 to 2026
$2.6M
Howard Hughes Medical InstituteNCI NIH HHS U01 CA200147NIAID NIH HHS T32 AI055403NIGMS NIH HHS R01 GM137117
6 · The paper itself

Abstract

Stress-induced readthrough transcription results in the synthesis of downstream-of-gene (DoG)-containing transcripts. The mechanisms underlying DoG formation during cellular stress remain unknown. Nascent transcription profiles during DoG induction in human cell lines using TT-TimeLapse sequencing revealed widespread transcriptional repression upon hyperosmotic stress. Yet, DoGs are produced regardless of the transcriptional level of their upstream genes. ChIP sequencing confirmed that stress-induced redistribution of RNA polymerase (Pol) II correlates with the transcriptional output of genes. Stress-induced alterations in the Pol II interactome are observed by mass spectrometry. While certain cleavage and polyadenylation factors remain Pol II associated, Integrator complex subunits dissociate from Pol II under stress leading to a genome-wide loss of Integrator on DNA. Depleting the catalytic subunit of Integrator using siRNAs induces hundreds of readthrough transcripts, whose parental genes partially overlap those of stress-induced DoGs. Our results provide insights into the mechanisms underlying DoG production and how Integrator activity influences DoG transcription.

Indexed as

Osmotic PressureSalt StressTranscriptional ActivationTranscription, GeneticDown-RegulationEndoribonucleasesHEK293 CellsHumansRNARNA Polymerase IITime FactorsEndoribonucleasesINTS11 protein, humanRNARNA Polymerase IIdownstream-of-gene transcriptshyperosmotic stressIntegrator complexRNA polymerase IIstress responseTransient Transcriptome TimeLapse sequencing

Identifiers

PMID33400923
PMCPMC7867636
OpenAlexW3118891438

What OpenQuestion holds

Textmetadata
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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.