Transcription without XPB Establishes a Unified Helicase-Independent Mechanism of Promoter Opening in Eukaryotic Gene Expression

• DOI: 10.1016/j.molcel.2017.01.012
• Publication Date: 2017-02-03T11:01:00Z
• Authors: Sergey Alekseev; Zita Nagy; Jérémy Sandoz; Amélie Weiss; Jean-Marc Egly; Nicolas Le May; Frederic Coin
• Keywords: Adenosine Triphosphatases; 0303 health sciences; Transcription, Genetic; Sequence Analysis, RNA; Gene Expression Profiling; DNA Helicases; Cell Line; DNA-Binding Proteins; 03 medical and health sciences; Mutation; Humans; Promoter Regions, Genetic; Transcription Factor TFIIH

Transcription starts with the assembly of pre-initiation complexes on promoters followed by their opening. Current models suggest that class II gene transcription requires ATP and the TFIIH XPB subunit to open a promoter. Here, we observe that XPB depletion surprisingly leaves transcription virtually intact. In contrast, inhibition of XPB ATPase activity affects transcription, revealing that mRNA expression paradoxically accommodates the absence of XPB while being sensitive to the inhibition of its ATPase activity. The XPB-depleted TFIIH complex is recruited to active promoters and contributes to transcription. We finally demonstrate that the XPB ATPase activity is only used to relieve a transcription initiation block imposed by XPB itself. In the absence of this block, transcription initiation can take place without XPB ATPase activity. These results suggest that a helicase is dispensable for mRNA transcription, thereby unifying the mechanism of promoter DNA opening for the three eukaryotic RNA polymerases.