Structural basis of TFIIIC-dependent RNA polymerase III transcription initiation

Mol Cell. 2023 Aug 3;83(15):2641-2652.e7. doi: 10.1016/j.molcel.2023.06.015. Epub 2023 Jul 3.

Abstract

RNA polymerase III (Pol III) is responsible for transcribing 5S ribosomal RNA (5S rRNA), tRNAs, and other short non-coding RNAs. Its recruitment to the 5S rRNA promoter requires transcription factors TFIIIA, TFIIIC, and TFIIIB. Here, we use cryoelectron microscopy (cryo-EM) to visualize the S. cerevisiae complex of TFIIIA and TFIIIC bound to the promoter. Gene-specific factor TFIIIA interacts with DNA and acts as an adaptor for TFIIIC-promoter interactions. We also visualize DNA binding of TFIIIB subunits, Brf1 and TBP (TATA-box binding protein), which results in the full-length 5S rRNA gene wrapping around the complex. Our smFRET study reveals that the DNA within the complex undergoes both sharp bending and partial dissociation on a slow timescale, consistent with the model predicted from our cryo-EM results. Our findings provide new insights into the transcription initiation complex assembly on the 5S rRNA promoter and allow us to directly compare Pol III and Pol II transcription adaptations.

Keywords: FRET; RNA polymerase III; TFIIIA; TFIIIB; TFIIIC; cryo-EM; transcription.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cryoelectron Microscopy
  • DNA / metabolism
  • RNA Polymerase III / genetics
  • RNA Polymerase III / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Transcription Factor TFIIIA / genetics
  • Transcription Factor TFIIIA / metabolism
  • Transcription Factor TFIIIB / genetics
  • Transcription Factor TFIIIB / metabolism
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism
  • Transcription, Genetic*

Substances

  • transcription factor TFIIIC
  • Transcription Factors
  • Transcription Factor TFIIIB
  • RNA Polymerase III
  • Transcription Factor TFIIIA
  • DNA