Control of RNA polymerase II activity by dedicated CTD kinases and phosphatases

The elongation phase of eukaryotic transcription by RNA polymerase II (RNAPII) is an important target for regulation of gene expression. An interplay of positive and negative elongation factors determines the elongation activity of RNAPII in different promoters. The phosphorylation status of the carboxyl-terminal-domain (CTD) of the larger subunit of RNAPII appears to be the regulatory focus of different factors regulating mRNA processivity. The emerging model of the transcription cycle proposes that the phosphorylation state of the CTD is dynamic during elongation with different forms predominating at different stages of transcription. Shortly after initiation RNA polymerase II comes under the control of negative elongation factors and enters abortive elongation. Escape from the action of these negative controls requires the action of at least one positive elongation factor identified in the P-TEFb complex composed of the Cyclin-Dependent Kinase CDK9 and its regulatory subunit cyclin T. Finally, the requirement of CTD phosphatase activity, identified in the FCP1 protein, has been invoked as necessary to recycle the hypophosphorylated form of the RNA polymerase II competent to reinitiate the transcription cycle.