Updating the rna polymerase ctd code
The CTD kinases CDK7 and CDK9 phosphorylate CTD Ser-5/7 and Ser-2/5, respectively (7).
CDK7 phosphorylation of Ser-5 is associated with transcription initiation, RNA capping, and histone modifications, whereas CDK9 phosphorylation of Ser-2/5 is associated with elongation, splicing, and DNA repair (8).
An inhibitor of CDK9 and CDK7 CTD kinase activities, TAF7 also binds to BRD4 and inhibits its kinase activity.
BRD4 phosphorylates PTEFb/CDK9 at either Thr-29 or Thr-186, depending on its relative abundance, which represses or activates CDK9 CTD kinase activity, respectively.
Conversely, CDK9 phosphorylates BRD4 enhancing its CTD kinase activity.
The mechanisms regulating the kinases that establish these phosphorylation patterns on the CTD are not known.
We report that three CTD kinases, CDK7, CDK9, and BRD4, engage in cross-talk, modulating their subsequent CTD phosphorylation.
Thus, a complex regulatory network governs Pol II CTD kinases. CTD phosphorylation dictates many Pol II interactions and is a critical step during eukaryotic transcription (1, 2).
It not only triggers co-transcriptional RNA capping and splicing, but also couples transcription with DNA repair, chromatin remodeling, and RNA transport (3).
The RNA polymerase II (Pol II) C-terminal domain (CTD) serves as a docking site for numerous proteins, bridging various nuclear processes to transcription.
The recruitment of these proteins is mediated by CTD phospho-epitopes generated during transcription.
Conclusion: CTD kinases regulate each other both directly and indirectly through TAF7.
Significance: CTD kinase cross-talk indicates a novel mechanism for ensuring orderly, sequential phosphorylation of Pol II CTD.
Background: The RNA polymerase II C-terminal domain (CTD) recruits RNA processing complexes spatio-temporally through its phosphorylation patterns.