Structural visualization of transcription initiation in action

Science. 2023 Dec 22;382(6677):eadi5120. doi: 10.1126/science.adi5120. Epub 2023 Dec 22.

Abstract

Transcription initiation is a complex process, and its mechanism is incompletely understood. We determined the structures of de novo transcribing complexes TC2 to TC17 with RNA polymerase II halted on G-less promoters when nascent RNAs reach 2 to 17 nucleotides in length, respectively. Connecting these structures generated a movie and a working model. As initially synthesized RNA grows, general transcription factors (GTFs) remain bound to the promoter and the transcription bubble expands. Nucleoside triphosphate (NTP)-driven RNA-DNA translocation and template-strand accumulation in a nearly sealed channel may promote the transition from initially transcribing complexes (ITCs) (TC2 to TC9) to early elongation complexes (EECs) (TC10 to TC17). Our study shows dynamic processes of transcription initiation and reveals why ITCs require GTFs and bubble expansion for initial RNA synthesis, whereas EECs need GTF dissociation from the promoter and bubble collapse for promoter escape.

MeSH terms

  • Animals
  • Cryoelectron Microscopy
  • DNA-Directed RNA Polymerases / chemistry
  • Humans
  • Motion Pictures
  • RNA Polymerase II / chemistry
  • RNA* / biosynthesis
  • Sus scrofa
  • Transcription Factors, General* / metabolism
  • Transcription Initiation, Genetic*

Substances

  • DNA-Directed RNA Polymerases
  • RNA
  • RNA Polymerase II
  • Transcription Factors, General