In eukaryotic transcription, RNA polymerase II transcribes mRNA precursors. Which covalent modification of the CTD (C-terminal domain) of RNA Pol II switches it from the promoter-bound preinitiation state to productive elongation?
- A Phosphorylation of Ser5 of the CTD heptapeptide repeat by TFIIH-associated CDK7
- B Ubiquitination of CTD lysine residues by WWP2
- C Phosphorylation of Ser2 of the CTD heptapeptide repeat by P-TEFb (CDK9) ✓
- D Acetylation of CTD by p300/CBP
Explanation
RNA Pol II CTD contains tandem heptapeptide repeats (YSPTSPS). CTD phosphorylation status governs the transcription cycle. Ser5 phosphorylation by TFIIH-CDK7 occurs at promoter clearance/capping (5' cap addition). After promoter escape, RNA Pol II often pauses ~30–50 nt downstream at the promoter-proximal pause point (enforced by NELF and DSIF). Productive elongation requires P-TEFb (CDK9/cyclin T) which phosphorylates Ser2 of the CTD and phosphorylates NELF (causing its dissociation) and DSIF (converting it to a positive elongation factor). Ser2 phosphorylation by P-TEFb is the critical switch from paused to productive elongation, and also recruits RNA processing and termination factors. Ubiquitination and acetylation of CTD are not established regulatory switches.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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