Structural basis of transcription: backtracked RNA polymerase II at 3.4 angstrom resolution

Science. 2009 May 29;324(5931):1203-6. doi: 10.1126/science.1168729.

Abstract

Transcribing RNA polymerases oscillate between three stable states, two of which, pre- and posttranslocated, were previously subjected to x-ray crystal structure determination. We report here the crystal structure of RNA polymerase II in the third state, the reverse translocated, or "backtracked" state. The defining feature of the backtracked structure is a binding site for the first backtracked nucleotide. This binding site is occupied in case of nucleotide misincorporation in the RNA or damage to the DNA, and is termed the "P" site because it supports proofreading. The predominant mechanism of proofreading is the excision of a dinucleotide in the presence of the elongation factor SII (TFIIS). Structure determination of a cocrystal with TFIIS reveals a rearrangement whereby cleavage of the RNA may take place.

Publication types

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

MeSH terms

  • Base Pair Mismatch
  • Crystallography, X-Ray
  • Guanosine Monophosphate / chemistry
  • Guanosine Monophosphate / metabolism
  • Models, Molecular
  • Nucleic Acid Conformation
  • Oligoribonucleotides / chemistry
  • Oligoribonucleotides / metabolism*
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • RNA / chemistry
  • RNA / metabolism*
  • RNA Polymerase II / chemistry*
  • RNA Polymerase II / metabolism*
  • Saccharomyces cerevisiae / enzymology*
  • Transcription, Genetic*
  • Transcriptional Elongation Factors / chemistry
  • Transcriptional Elongation Factors / metabolism*

Substances

  • Oligoribonucleotides
  • Transcriptional Elongation Factors
  • transcription factor S-II
  • RNA
  • Guanosine Monophosphate
  • RNA Polymerase II

Associated data

  • PDB/3GTG
  • PDB/3GTJ
  • PDB/3GTK
  • PDB/3GTM