Transcription elongation by RNA polymerase II (RNAPII) is controlled by a number of trans-acting transcription elongation factors as well as by cis-acting elements. Transcription elongation is a rate-limiting step for proper mRNA production in which the phosphorylation of Pol II CTD is a crucial biochemical event. The role of CTD phosphorylation in transcription by Pol II is greatly impaired by protein kinase inhibitors such as 5,6-dichloro-1- ribofuranosylbenzimidazole (DRB), which block CTD phosphorylation and induce arrest of elongating Pol II. DRB-sensitive activation Pol II CTD during elongation has enabled the isolation of two sets of factors -Negative Elongation Factors (NELF) and DRB sensitivity inducing factor (DSIF). P-Tefb is a DRB-sensitive, cyclin-dependent CTD kinase composed of Cdk9 that carries out Serine-2 phosphorylation of Pol II CTD during elongation.
The mechanism by which DSIF, NELF and P-TEFb act together in Pol II-regulated elongation is yet to be fully understood. Various biochemical evidences point to a model in which DSIF and NELF negatively regulate elongation through interactions with polymerase containing a hypophosphorylated CTD. Subsequent phosphorylation of the Pol II CTD by P-Tefb might promote elongation by inhibiting interactions of DSIF and NELF with the elongation complex.