Direct targeting and regulation of RNA polymerase II by cell signaling kinases

Distinct phosphorylation marks are placed on the carboxyl-terminal domain (CTD) of RNA polymerase II (Pol II) during different stages of gene transcription. These phospho-CTD marks function as a molecular recognition code for the recruitment of stage-specific effector proteins. Querying ~80% of the human kinome, we identified 117 kinases that phosphorylate the CTD with a high degree of positional selectivity. The unifying characteristic linking these diverse kinases is that they selectively regulate Pol II at signal-responsive genes. An example of such "direct-at-gene" Pol II regulation is displayed by epidermal growth factor receptor (EGFR), a cell surface receptor tyrosine kinase. More broadly, our atlas of CTD kinases implicates Pol II as a direct regulatory end point for signal-transducing kinases that govern cellular physiology and contribute to the etiology of numerous diseases.

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Publication Details

Journal
Science
Published
2025-11-06
DOI
https://doi.org/10.1126/science.ads7152
Citations
2
Primary Topic
Genomics and Chromatin Dynamics
Type
article
Field-Weighted Citation Impact
1.61
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article

Direct targeting and regulation of RNA polymerase II by cell signaling kinases

Taosheng Chen, Yuan Zhi, Shondra M. Pruett‐Miller, Gang Wu et al.
2 citations
Science
Genomics and Chromatin Dynamics
1.61
article

Direct targeting and regulation of RNA polymerase II by cell signaling kinases

Taosheng Chen, Yuan Zhi, Shondra M. Pruett‐Miller, Gang Wu, Patrick Fernandes Rodrigues, Walter H. Lang, Meritxell B. Cutrona, Beisi Xu, Aseem Z. Ansari, Preeti Dabas, Ryan P. Kempen, Wojciech Rosikiewicz, Adithi Danda, John J. Bowling, Mollie S. Prater
article en
2 citations

Abstract

Distinct phosphorylation marks are placed on the carboxyl-terminal domain (CTD) of RNA polymerase II (Pol II) during different stages of gene transcription. These phospho-CTD marks function as a molecular recognition code for the recruitment of stage-specific effector proteins. Querying ~80% of the human kinome, we identified 117 kinases that phosphorylate the CTD with a high degree of positional selectivity. The unifying characteristic linking these diverse kinases is that they selectively regulate Pol II at signal-responsive genes. An example of such "direct-at-gene" Pol II regulation is displayed by epidermal growth factor receptor (EGFR), a cell surface receptor tyrosine kinase. More broadly, our atlas of CTD kinases implicates Pol II as a direct regulatory end point for signal-transducing kinases that govern cellular physiology and contribute to the etiology of numerous diseases.

ScienceVol. 390(6773)
St. Jude Children's Research Hospital (US)
Openalex Percentile: Top 14%
Genomics and Chromatin Dynamics
1.61
DOISourceOpenAlex
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Direct targeting and regulation of RNA polymerase II by cell signaling kinases — Taosheng Chen, Yuan Zhi, et al. · Science (2025) | TGRS Research Map | TGRS