Evidence map›Paper›PMID 39829884›Full record

ArticlebioRxiv : the preprint server for biology2025

Multi-omics and biochemical reconstitution reveal CDK7-dependent mechanisms controlling RNA polymerase II function at gene 5'- and 3'-ends.

Olivia Luyties, Lynn Sanford, Jessica Rodino, Michael Nagel, Taylor Jones, Jenna K Rimel, Christopher C Ebmeier, Grace S Shelby, Kira Cozzolino, Finn Brennan and 7 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Olivia LuytiesDept. of Biochemistry, University of Colorado; Boulder, CO, 80303, USA.
Lynn SanfordDept. of Molecular, Cellular, and Developmental Biology, University of Colorado; Boulder, CO, 80303, USA.
Jessica RodinoDept. of Biochemistry, University of Colorado; Boulder, CO, 80303, USA.
Michael NagelDept. of Biochemistry, University of Colorado; Boulder, CO, 80303, USA.
Taylor JonesDept. of Biochemistry, University of Colorado; Boulder, CO, 80303, USA.
Jenna K RimelDept. of Biochemistry, University of Colorado; Boulder, CO, 80303, USA.
Christopher C EbmeierDept. of Biochemistry, University of Colorado; Boulder, CO, 80303, USA.
Grace S ShelbyDept. of Biochemistry, University of Colorado; Boulder, CO, 80303, USA.
Kira CozzolinoDept. of Biochemistry, University of Colorado; Boulder, CO, 80303, USA.
Finn BrennanDept. of Biochemistry, University of Colorado; Boulder, CO, 80303, USA.
Axel HartzogDept. of Biochemistry, University of Colorado; Boulder, CO, 80303, USA.
Mirzam B SaucedoDept. of Biochemistry, University of Colorado; Boulder, CO, 80303, USA.
Lotte P WattsDept. of Biochemistry, University of Colorado; Boulder, CO, 80303, USA.
Sabrina SpencerDept. of Biochemistry, University of Colorado; Boulder, CO, 80303, USA.
Jennifer F KugelDept. of Biochemistry, University of Colorado; Boulder, CO, 80303, USA.
Robin D DowellDept. of Molecular, Cellular, and Developmental Biology, University of Colorado; Boulder, CO, 80303, USA.
Dylan J TaatjesDept. of Biochemistry, University of Colorado; Boulder, CO, 80303, USA.

Funding

Supplemental request for MAX-TL Ultracentrifuge and rotorR35GM139550 · NIGMS · UNIVERSITY OF COLORADO · PI Dylan J Taatjes · 2021 to 2026
$3.8M
Unraveling the biological roles of specific miRNAs, from experimental target identification through functional characterizationR01GM148613 · NIGMS · UNIVERSITY OF COLORADO · PI Jennifer F. Kugel · 2023 to 2026
$1.3M
Q Exactive HF Nanoflow LC Mass Spectrometry SystemS10OD025267 · OD · UNIVERSITY OF COLORADO · PI AHN, NATALIE G. · 2018 to 2018
$600k
How do CDK7 and CDK9 regulate Pol II initiation and pausing?F31CA254478 · NCI · UNIVERSITY OF COLORADO · PI LUYTIES, OLIVIA CARON · 2020 to 2022
$115k
NCI NIH HHS F31 CA254478NIGMS NIH HHS R01 GM148613NIGMS NIH HHS R35 GM139550NIH HHS S10 OD025267
6 · The paper itself

Abstract

CDK7 regulates RNA polymerase II (RNAPII) initiation, elongation, and termination through incompletely understood mechanisms. Because contaminating kinases precluded CDK7 analysis with nuclear extracts, we completed biochemical assays with purified factors. Reconstitution of RNAPII transcription initiation showed CDK7 inhibition slowed and/or paused RNAPII promoter-proximal transcription, which reduced re-initiation. These CDK7-regulatory functions were Mediator- and TFIID-dependent. Similarly in human cells, CDK7 inhibition reduced transcription by suppressing RNAPII activity at promoters, consistent with reduced initiation and/or re-initiation. Moreover, widespread 3'-end readthrough transcription was observed in CDK7-inhibited cells; mechanistically, this occurred through rapid nuclear depletion of RNAPII elongation and termination factors, including high-confidence CDK7 targets. Collectively, these results define how CDK7 governs RNAPII function at gene 5'-ends and 3'-ends, and reveal that nuclear abundance of elongation and termination factors is kinase-dependent. Because 3'-readthrough transcription is commonly induced during stress, our results further suggest regulated suppression of CDK7 activity may enable this RNAPII transcriptional response.

Identifiers

PMID39829884
PMCPMC11741307

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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.