Evidence map›Paper›PMID 31385803›Full record

ArticleeLife2019

Tyr1 phosphorylation promotes phosphorylation of Ser2 on the C-terminal domain of eukaryotic RNA polymerase II by P-TEFb.

Joshua E Mayfield, Seema Irani, Edwin E Escobar, Zhao Zhang, Nathaniel T Burkholder, Michelle R Robinson, M Rachel Mehaffey, Sarah N Sipe, Wanjie Yang, Nicholas A Prescott and 4 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

32 citing papers in PubMed, 40 citations in OpenAlex.

  1. Review
  2. Review
  3. Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026
    Review
  4. Article
  5. Review
  6. Article
  7. Article
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  13. Structural basis of Cdk7 activation by dual T-loop phosphorylation.bioRxiv : the preprint server for biology · 2024
    Article
  14. Article
  15. Article
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  17. Article
  18. Function-guided proximity mapping unveils electrophilic-metabolite sensing by proteins not present in their canonical locales.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  19. Targeting transcription cycles in cancer.Nature reviews. Cancer · 2022
    Review
  20. Article
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

14 authors at 2 institutions in 1 country.

Joshua E Mayfield *Department of Molecular Biosciences, University of Texas at Austin, Austin, United States.
Seema Irani *Department of Chemical Engineering, University of Texas at Austin, Austin, United States.ORCID 0000-0001-5159-3473
Edwin E EscobarDepartment of Chemistry, University of Texas at Austin, Austin, United States.ORCID 0000-0002-0086-6264
Zhao ZhangDepartment of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, United States.
Nathaniel T BurkholderDepartment of Molecular Biosciences, University of Texas at Austin, Austin, United States.
Michelle R RobinsonDepartment of Chemistry, University of Texas at Austin, Austin, United States.
M Rachel MehaffeyDepartment of Chemistry, University of Texas at Austin, Austin, United States.
Sarah N SipeDepartment of Chemistry, University of Texas at Austin, Austin, United States.ORCID 0000-0003-4554-7571
Wanjie YangDepartment of Molecular Biosciences, University of Texas at Austin, Austin, United States.
Nicholas A PrescottDepartment of Molecular Biosciences, University of Texas at Austin, Austin, United States.ORCID 0000-0002-0635-8906
Karan R KathuriaDepartment of Molecular Biosciences, University of Texas at Austin, Austin, United States.
Zhijie LiuDepartment of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, United States.
Jennifer S BrodbeltDepartment of Chemistry, University of Texas at Austin, Austin, United States.ORCID 0000-0003-3207-0217
Yan ZhangDepartment of Molecular Biosciences, University of Texas at Austin, Austin, United States.ORCID 0000-0002-9360-5388
The University of Texas at Austin · USThe University of Texas Health Science Center at San Antonio · US

Funding

Gene-specific transcriptional silencing directed by dephosphorylation of RNAP IIR01GM104896 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI ZHANG, YAN JESSIE · 2013 to 2022
$2.4M
Interpretation of the phosphorylation code of RNA polymerase II during eukaryotic transcriptionR01GM125882 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI BRODBELT, JENNIFER S., ZHANG, YAN JESSIE · 2018 to 2021
$1.4M
Mapping the C Terminal Domain of RNA Polymerase II by UVPD Mass SpectrometryR21EB018391 · NIBIB · UNIVERSITY OF TEXAS AT AUSTIN · PI BRODBELT, JENNIFER S. · 2014 to 2015
$405k
NIBIB NIH HHS R21 EB018391NIBIB NIH HHS R21EB018391NIGMS NIH HHS R01 GM104896NIGMS NIH HHS R01 GM125882NIGMS NIH HHS R01 RM125882Welch Foundation F-1155Welch Foundation F-1778
6 · The paper itself

Abstract

The Positive Transcription Elongation Factor b (P-TEFb) phosphorylates Ser2 residues of the C-terminal domain (CTD) of the largest subunit (RPB1) of RNA polymerase II and is essential for the transition from transcription initiation to elongation in vivo. Surprisingly, P-TEFb exhibits Ser5 phosphorylation activity in vitro. The mechanism garnering Ser2 specificity to P-TEFb remains elusive and hinders understanding of the transition from transcription initiation to elongation. Through in vitro reconstruction of CTD phosphorylation, mass spectrometry analysis, and chromatin immunoprecipitation sequencing (ChIP-seq) analysis, we uncover a mechanism by which Tyr1 phosphorylation directs the kinase activity of P-TEFb and alters its specificity from Ser5 to Ser2. The loss of Tyr1 phosphorylation causes an accumulation of RNA polymerase II in the promoter region as detected by ChIP-seq. We demonstrate the ability of Tyr1 phosphorylation to generate a heterogeneous CTD modification landscape that expands the CTD's coding potential. These findings provide direct experimental evidence for a combinatorial CTD phosphorylation code wherein previously installed modifications direct the identity and abundance of subsequent coding events by influencing the behavior of downstream enzymes.

Indexed as

Protein Processing, Post-TranslationalHumansPhosphorylationPositive Transcriptional Elongation Factor BRNA Polymerase IISerineTranscription, GeneticTyrosinePositive Transcriptional Elongation Factor BRNA Polymerase IISerineTyrosinebiochemistrychemical biologyhumanphosphorylationpost-translational modificationpromoter-proximal pausingP-TEFbtranscriptionultraviolet photodissociation mass spectrometry

Identifiers

PMID31385803
PMCPMC6715403
OpenAlexW2966394534

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.