Which transcription factor is required to release RNA polymerase II from promoter-proximal pausing into productive elongation?

• A. DNA polymerase
• B. P-TEFb
• C. RNA helicase
• D. Ligase

Answer: (B)

Promoter-proximal pausing is a checkpoint where RNA polymerase II sits near the start of a gene after initiating transcription. The release into productive elongation is driven by P-TEFb, a kinase complex (CDK9 and Cyclin T) that phosphorylates multiple targets to switch Pol II from pausing to elongation. It phosphorylates the RS domain of the RNA Pol II CTD at Ser2, promoting a switch to processive elongation. It also phosphorylates the pausing factors DSIF and NELF: NELF is released upon phosphorylation, and DSIF helps convert into a positive elongation factor, supporting the efficient elongation of the transcript. Without this phosphorylation by P-TEFb, RNA Pol II remains paused and transcripts stay short.

The other proteins listed don’t regulate this transition: DNA polymerase is involved in copying DNA, not transcription; RNA helicase unwinds RNA structures but doesn’t control promoter-proximal pausing; ligase seals DNA breaks.