Three human RNA polymerases interact with TFIIH via a common RPB6 subunit

Area of Science:

• Molecular Biology
• Gene Transcription
• DNA Repair

Background:

• Eukaryotes utilize three RNA polymerases (RNAPs) for diverse RNA synthesis.
• A common subunit, RPB6, in all RNAPs has a flexible N-terminal tail (NTT) with an unclear function.

Purpose of the Study:

• To elucidate the function of the RPB6 N-terminal tail (NTT).
• To investigate the interaction between RPB6 NTT and the general transcription/repair factor TFIIH.

Main Methods:

• Nuclear magnetic resonance (NMR) to determine RPB6 structures.
• Modeling of RNAPII-TFIIH complexes using cryo-electron microscopy (cryo-EM) data.
• Analysis of point mutations in RPB6 NTT.

Main Results:

• The RPB6 NTT directly interacts with the PH domain of TFIIH's p62 subunit.
• This interaction is crucial for recruiting TFIIH to transcription sites for transcription-coupled nucleotide excision repair (TC-NER) in RNAPI and RNAPII genes.
• Mutations in RPB6 NTT significantly impair transcription by all three RNAPs.

Conclusions:

• The p62-RPB6 interaction is vital for transcription, TC-NER, and cell proliferation.
• TFIIH is implicated in the regulatory mechanisms of all eukaryotic RNA polymerase systems.