Structural basis of RNA polymerase III transcription initiation

Nature. 2018 Jan 17;553(7688):301-306. doi: 10.1038/nature25441.

Abstract

RNA polymerase (Pol) III transcribes essential non-coding RNAs, including the entire pool of transfer RNAs, the 5S ribosomal RNA and the U6 spliceosomal RNA, and is often deregulated in cancer cells. The initiation of gene transcription by Pol III requires the activity of the transcription factor TFIIIB to form a transcriptionally active Pol III preinitiation complex (PIC). Here we present electron microscopy reconstructions of Pol III PICs at 3.4-4.0 Å and a reconstruction of unbound apo-Pol III at 3.1 Å. TFIIIB fully encircles the DNA and restructures Pol III. In particular, binding of the TFIIIB subunit Bdp1 rearranges the Pol III-specific subunits C37 and C34, thereby promoting DNA opening. The unwound DNA directly contacts both sides of the Pol III cleft. Topologically, the Pol III PIC resembles the Pol II PIC, whereas the Pol I PIC is more divergent. The structures presented unravel the molecular mechanisms underlying the first steps of Pol III transcription and also the general conserved mechanisms of gene transcription initiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cryoelectron Microscopy
  • DNA / chemistry
  • DNA / metabolism
  • DNA / ultrastructure
  • Models, Molecular
  • Nucleic Acid Conformation
  • Promoter Regions, Genetic
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • RNA Polymerase I / chemistry
  • RNA Polymerase II / chemistry
  • RNA Polymerase III / chemistry
  • RNA Polymerase III / metabolism*
  • RNA Polymerase III / ultrastructure*
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / ultrastructure
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / ultrastructure
  • Templates, Genetic
  • Transcription Factor TFIIIB / chemistry
  • Transcription Factor TFIIIB / metabolism
  • Transcription Factor TFIIIB / ultrastructure
  • Transcription Factors, TFII / chemistry
  • Transcription Initiation, Genetic*

Substances

  • Bdp1 protein, S cerevisiae
  • Protein Subunits
  • Saccharomyces cerevisiae Proteins
  • Transcription Factor TFIIIB
  • Transcription Factors, TFII
  • transcription factor TFIIE
  • DNA
  • RNA Polymerase II
  • RNA Polymerase I
  • RNA Polymerase III
  • transcription factor TFIIF