Evidence map›Paper›PMID 34520723›Full record

ArticleMolecular cell2021

STL-seq reveals pause-release and termination kinetics for promoter-proximal paused RNA polymerase II transcripts.

Joshua T Zimmer, Nicolle A Rosa-Mercado, Daniele Canzio, Joan A Steitz, Matthew D Simon

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 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

31 citing papers in PubMed, 41 citations in OpenAlex.

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  11. Molecular Mechanisms of Sepsis-Associated Acute Kidney Injury.Journal of the American Society of Nephrology : JASN · 2025
    Review
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  16. Metabolic labeling of RNA using ribonucleoside analogs enables the evaluation of RNA synthesis and degradation rates.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2025
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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

5 authors at 3 institutions in 1 country.

Joshua T ZimmerDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA; Institute for Biomolecular Design and Discovery, Yale University, West Haven, CT 06516, USA.
Nicolle A Rosa-MercadoDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA.
Daniele CanzioDepartment of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA.
Joan A SteitzDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT 06536, USA.
Matthew D SimonDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA; Institute for Biomolecular Design and Discovery, Yale University, West Haven, CT 06516, USA. Electronic address: matthew.simon@yale.edu.
Yale University · USHoward Hughes Medical Institute · USUniversity of California, San Francisco · US

Funding

Skill Development for Diverse Scientific Careers: A New Course Predoctoral Program in Cellular and Molecular BiologyT32GM007223 · NIGMS · YALE UNIVERSITY · PI BASERGA, SUSAN J · 1985 to 2019
$31.0M
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
Integrating RNAs into signaling pathways by engineering covalent RNA modificationDP2HD083992 · NICHD · YALE UNIVERSITY · PI SIMON, MATTHEW DAVID · 2014 to 2014
$2.5M
NCI NIH HHS U01 CA200147NIAID NIH HHS T32 AI055403NICHD NIH HHS DP2 HD083992NIGMS NIH HHS R01 GM137117NIGMS NIH HHS T32 GM007223
6 · The paper itself

Abstract

Despite the critical regulatory function of promoter-proximal pausing, the influence of pausing kinetics on transcriptional control remains an active area of investigation. Here, we present Start-TimeLapse-seq (STL-seq), a method that captures the genome-wide kinetics of short, capped RNA turnover and reveals principles of regulation at the pause site. By measuring the rates of release into elongation and premature termination through the inhibition of pause release, we determine that pause-release rates are highly variable, and most promoter-proximal paused RNA polymerase II molecules prematurely terminate (∼80%). The preferred regulatory mechanism upon a hormonal stimulus (20-hydroxyecdysone) is to influence pause-release rather than termination rates. Transcriptional shutdown occurs concurrently with the induction of promoter-proximal termination under hyperosmotic stress, but paused transcripts from TATA box-containing promoters remain stable, demonstrating an important role for cis-acting DNA elements in pausing. STL-seq dissects the kinetics of pause release and termination, providing an opportunity to identify mechanisms of transcriptional regulation.

Indexed as

Gene Expression RegulationPromoter Regions, GeneticSequence Analysis, RNADNA MethylationEcdysteroneGene Expression ProfilingGenetic TechniquesGenomeHormonesKineticsMutationOsmosisProtein BindingRNA, MessengerRNA Polymerase IISignal TransductionEcdysteroneHormonesRNA, MessengerRNA Polymerase IIpremature terminationpromoter-proximal pausingrelease into elongationscRNASTL-seqTimeLapse

Identifiers

PMID34520723
PMCPMC9020433
OpenAlexW3201177971

What OpenQuestion holds

Textmetadata
LicenceTDM
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.