TFIIH Phosphorylation Inhibition: Which Transcription Step Is Most Affected?

7. A highly specific inhibitor that targets the phosphorylation activity of TFIIH is added to an in vitro transcription reaction. Which one of the following steps is most likely to be affected?
   (1) Binding of RNA polymerase to promoter sequence
   (2) Promoter clearance
   (3) Recruitment of TFIID
   (4) Open promoter complex formation

Slug: tfIIh-phosphorylation-inhibition-transcription-step

Meta Description:
Discover which step of eukaryotic transcription is most affected by inhibition of TFIIH phosphorylation activity. Get the right CSIR NET Life Science answer, and learn how Let’s Talk Academy empowers aspirants with free PYQs, video solutions, and study materials.

Correct Answer

(2) Promoter clearance

Detailed Explanation

TFIIH is a multifunctional general transcription factor essential for transcription initiation by RNA polymerase II in eukaryotes. One of its key roles is to phosphorylate the C-terminal domain (CTD) of RNA polymerase II via its kinase activity (mainly through the CDK7 subunit). This phosphorylation is a critical regulatory event that allows RNA polymerase II to transition from the initiation phase to the elongation phase—a process known as promoter clearance.

Why Promoter Clearance Is Most Affected

• Promoter Clearance Defined:
  Promoter clearance is the step where RNA polymerase II escapes the promoter after synthesizing the first few nucleotides, transitioning into productive elongation.

• Role of TFIIH Phosphorylation:
  The phosphorylation of the RNA polymerase II CTD by TFIIH is essential for releasing the polymerase from the promoter-bound pre-initiation complex. Without this phosphorylation, RNA polymerase II remains stalled at the promoter and cannot efficiently proceed into elongation.

• Experimental Evidence:
  Inhibition of TFIIH’s kinase activity specifically blocks this transition, causing an accumulation of transcription complexes at the promoter and a failure to produce full-length transcripts.

Why Other Steps Are Less Affected

• Binding of RNA polymerase to promoter sequence and Recruitment of TFIID occur before TFIIH’s kinase activity is required.

• Open promoter complex formation involves DNA unwinding and is primarily dependent on TFIIH’s helicase activity, not its kinase function.

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Summary:
A highly specific inhibitor of TFIIH phosphorylation activity will most severely affect promoter clearance (option 2), blocking the transition of RNA polymerase II into productive elongation. Trust Let’s Talk Academy for the best free CSIR NET Life Science preparation resources.