Phosphorylation of RNAPII

Abstract

The C-terminal Domain of RNA polymerase II undergoes a cycle of phosphorylation which allows it to temporally couple transcription and transcription-associated processes. The discovery of hitherto unrecognized metazoan elongation phase CTD kinase activities expands our understanding of transcription. We discuss the circumstances that delayed the recognition of these kinase activities.

Acknowledgements

We thank D. Price, H. Phatnani and T. Winsor for critical reading of the manuscript. We also apologize to the researchers whose work could not be referenced due to space limitations. This work was supported by NIH grant GM040505 and Duke School of Medicine Bridging Funds to A.L.G.

Figures and Tables

Figure 1 An updated model of the “Phoshpo-CTD cycle” featuring major kinase activities and CTD-associated proteins in both yeast (y) and metazoa (m). RNA Polymerase II is illustrated at four positions within a gene, with the phosphorylation state of the CTD indicated by color. The phosphorylation status of the CTD dictates which sets of factors bind to the CTD, and proteins bound by a specific CTD phosphorylation state are shown in the appropriate color (examples of associated factors at each stage of transcription are given below the gene). Major CTD kinase activities are indicated for both yeast and metazoa and include the newly characterized metazoan ortholog of yeast Ctk1, mCDK12. Although mCDK9 and mCDK12 kinase activities are illustrated as having distinct boundaries, it seems likely that the activities overlap during early elongation (whether this is really the case remains to be determined). CTD phosphatases work in coordination with the CTD kinases throughout the “Phospho-CTD cycle” in order to shape the phosphorylation status of the CTD (reviewed in references 2 and 3).