Figure 1. The transcription cycle. RNA polymerases (RNAPs) have an intrinsic affinity for DNA. Promoter-specific DNA binding by RNAPs is facilitated by recruitment factors unique to each RNAP. Once RNAP binds promoter DNA it forms a stable complex with the closed duplex DNA (RPc). The formation of RPc promotes a conformational change between RNAP and the DNA that results in an intermediate complex (RPi) that rapidly converts to an open complex (RPo) by the melting of the DNA around the transcription start site by RNAP. The formation of RPo results in a ternary complex competent to catalyse RNA synthesis. However, most RNAPs engage in nonproductive cycles of abortive RNA synthesis. Transition into a productive cycle occurs when the RNA chain reaches a critical length. At this point, called promoter clearance, RNAP disengages from the promoter and elongates the RNA chain. During the elongation phase, RNAP is subject to DNA and protein influences that can effect the kinetics of RNA synthesis. Once RNAP reaches termination sequences in the DNA, the ternary complex dissociates liberating the newly formed RNA chain. The released RNAP can then recycle for a subsequent round of RNA synthesis.

Figure 2. The CTD platform. The unique C-terminal domain (CTD) of RNAP II serves as a platform for the sequential loading of RNA-processing factors. Once the RNA chain exits from its protected environment within RNAP, it becomes a substrate for modification by RNA capping enzyme, splicing factors and RNA cleavage and polyadenylation reactions. The phosphorylation state of the CTD dictates which RNA-processing factors can bind the CTD and modify the RNA. Specifically, phosphorylation of serine 5 of CTD during transcription initiation enables capping enzyme to bind the CTD and catalyse the ‘capping’ reaction. Subsequent to promoter clearance there is a change in the phosphorylation state of the CTD with a shift of phosphorylation to serine 2. This change probably triggers the release of capping enzyme and the concomitant association of other RNA-processing enzymes. RNA polyadenylation is coupled to termination of RNA synthesis. Following cleavage and polyadenylation of the RNA chain, RNAP II continues to transcribe. However, the newly synthesized RNA molecule does not have a cap. It is possible that the lack of a cap makes it susceptible to degradation by an exonuclease which eventually disrupts the ternary complex. The subsequent or concomitant dephosphorylation of the CTD enables RNAP II to recycle and initiate another round of RNA synthesis.