Transcription elongation is not a smooth ride along double stranded DNA, as RNA polymerase undergoes extensive co-transcriptional pausing during transcription elongation. In general, RNA polymerase II does not transcribe through a gene at a constant pace. Rather it pauses periodically at certain sequences, sometimes for long periods of time before resuming transcription. This pausing is especially pronounced at nucleosomes, and arises in part through the polymerase entering a transcriptionally incompetent backtracked state. The duration of these pauses ranges from seconds to minutes or longer, and exit from long-lived pauses can be promoted by elongation factors such as TFIIS.
This pausing is also sometimes used for proofreading; here the polymerase backs up, erases some of the RNA it has already made and has another go at transcription. In extreme cases, for example, when the polymerase encounters a damaged nucleotide, it comes to a complete halt. More often, an elongating polymerase is stalled near the promoter. Promoter-proximal pausing during early elongation is a commonly used mechanism for regulating genes poised to be expressed rapidly or in a coordinated fashion. Pausing is mediated by a complex called NELF (negative elongation factor) in collaboration with DSIF (DRB-sensitivity-inducing factor containing SPT4/SPT5). The blockage is released once the polymerase receives an activation signal, such as the phosphorylation of Ser-2 of CTD tail by P-TEFb. Other elongation factors such as ELL and TFIIS stimulate the rate of elongation by limiting the length of time that polymerase pauses.