Evidence map›Paper›PMID 32859893›Full record

ArticleNature communications2020

Distinct Cdk9-phosphatase switches act at the beginning and end of elongation by RNA polymerase II.

Pabitra K Parua, Sampada Kalan, Bradley Benjamin, Miriam Sansó, Robert P Fisher

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
4.4field-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

40 citing papers in PubMed, 69 citations in OpenAlex.

  1. Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026
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  17. mRNA initiation and termination are spatially coordinated.bioRxiv : the preprint server for biology · 2024
    Article
  18. Article
  19. Article
  20. Super-enhancers complexes zoom in transcription in cancer.Journal of experimental & clinical cancer research : CR · 2023
    Review
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 1 institution in 1 country.

Pabitra K ParuaDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029-6574, USA.
Sampada KalanDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029-6574, USA.
Bradley BenjaminDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029-6574, USA.
Miriam SansóDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029-6574, USA.ORCID http://orcid.org/0000-0002-0794-3840
Robert P FisherDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029-6574, USA. Robert.fisher@mssm.edu.ORCID http://orcid.org/0000-0001-9873-8457
Icahn School of Medicine at Mount Sinai · US

Funding

THE TISCH CANCER INSTITUTE - CANCER CENTER SUPPORT GRANTP30CA196521 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Deanna L Benson · 2015 to 2026
$35.4M
Cyclin-dependent kinase control of cell-division and transcription cyclesR35GM127289 · NIGMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ROBERT P FISHER · 2018 to 2026
$4.4M
NCI NIH HHS P30 CA196521NIGMS NIH HHS R35 GM127289
6 · The paper itself

Abstract

Reversible phosphorylation of Pol II and accessory factors helps order the transcription cycle. Here, we define two kinase-phosphatase switches that operate at different points in human transcription. Cdk9/cyclin T1 (P-TEFb) catalyzes inhibitory phosphorylation of PP1 and PP4 complexes that localize to 3' and 5' ends of genes, respectively, and have overlapping but distinct specificities for Cdk9-dependent phosphorylations of Spt5, a factor instrumental in promoter-proximal pausing and elongation-rate control. PP1 dephosphorylates an Spt5 carboxy-terminal repeat (CTR), but not Spt5-Ser666, a site between Kyrpides-Ouzounis-Woese (KOW) motifs 4 and 5, whereas PP4 can target both sites. In vivo, Spt5-CTR phosphorylation decreases as transcription complexes pass the cleavage and polyadenylation signal (CPS) and increases upon PP1 depletion, consistent with a PP1 function in termination first uncovered in yeast. Depletion of PP4-complex subunits increases phosphorylation of both Ser666 and the CTR, and promotes redistribution of promoter-proximally paused Pol II into gene bodies. These results suggest that switches comprising Cdk9 and either PP4 or PP1 govern pause release and the elongation-termination transition, respectively.

Indexed as

Cyclin-Dependent Kinase 9HCT116 CellsHumansNuclear ProteinsPhosphorylationPositive Transcriptional Elongation Factor BReceptors, Neuropeptide YRNA InterferenceRNA Polymerase IITranscriptional Elongation FactorsTranscription, GeneticCDK9 protein, humanCyclin-Dependent Kinase 9neuropeptide Y4 receptorNuclear ProteinsPositive Transcriptional Elongation Factor BReceptors, Neuropeptide YRNA Polymerase IISUPT5H protein, humanTranscriptional Elongation Factors

Identifiers

PMID32859893
PMCPMC7455706
OpenAlexW3082258871

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.