The positive transcription elongation factor,
P-TEFb, plays an essential role in the regulation of transcription by
RNA polymerase II (Pol II) in eukaryotes. Immediately following initiation Pol II becomes trapped in promoter proximal paused positions on the majority of human genes (Figure 1). P-TEFb is a cyclin dependent kinase that can phosphorylate the DRB sensitivity inducing factor (
DSIF) and
negative elongation factor (NELF), as well as the carboxyl terminal domain of the large subunit of Pol II and this causes the transition into productive elongation leading to the synthesis of mRNAs. P-TEFb is regulated in part by a reversible association with the
7SK snRNP. Treatment of cells with the P-TEFb inhibitors
DRB or
flavopidirol leads to loss of
mRNA production and ultimately cell death.