Phosphorylation of the C-terminal domain of RNA polymerase II.

The CTD has become a focal point in the analysis of RNAP II. The unusual properties of the CTD, including its unique structure and high level of phosphorylation, have stimulated interest in understanding the role this domain plays in the transcription of protein-coding genes. Research during the past ten years suggests that the CTD may function at multiple steps in the transcription cycle and that its involvement is promoter dependent. The general idea, for which there is now considerable support, is that the CTD mediates the interaction of RNAP II with the transcription apparatus and that these interactions are influenced by the phosphorylation that occurs throughout the CTD. The temporal relationship between phosphorylation of the CTD and the progression of RNAP II through the transcription cycle has been established in a general sense. However, it is not clear that the modifications that occur at a given time are causally related to the progression of RNAP II beyond that point in the transcription cycle. The idea that phosphorylation of the CTD mediates the release of RNAP II from the preinitiation complex is an attractive one and consistent with a number of experimental results. However, an increasing number of observations suggest that CTD phosphorylation and promoter clearance may not be causally related. One possibility is that even though phosphorylation occurs concomitant with transcript initiation it plays no real role in the initiation process and is necessary only to establish an elongation competent form of the enzyme. Alternatively, CTD phosphorylation may play an essential role in the release of RNAP II from preinitiation complexes in vivo but may be dispensable in defined in vitro transcription systems. Finally it may be important to distinguish between promoter clearance as defined by RNAP moving off the transcriptional start site and the complete disruption of interactions between RNAP II and the preinitiation complex. Because of the extended nature of the CTD, RNAP II may remain tethered to factors assembled on the promoter even though a short transcript has been synthesized. Clearly additional research is necessary to (a) define the contacts made by the CTD in preinitiation complexes, (b) understand the relationship between the disruption of these contacts and CTD phosphorylation and (c) understand biochemically what is required to generate an elongation competent form of RNAP II. The possibility that the CTD plays a role in transcript elongation has been proposed since the discovery of the CTD [15].(ABSTRACT TRUNCATED AT 400 WORDS)