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