Sequence-dependent Kinetic Model for Transcription Elongation by RNA Polymerase

J Mol Biol. 2004 Nov 19;344(2):335-49. doi: 10.1016/j.jmb.2004.08.107.

Abstract

We present a kinetic model for the sequence-dependent motion of RNA polymerase (RNAP) during transcription elongation. For each NTP incorporation, RNAP has a net forward translocation of one base-pair along the DNA template. However, this process may involve the exploration of back-tracked and forward-tracked translocation modes. In our model, the kinetic rates for the reaction pathway, calculated based on the stabilities of the transcription elongation complex (TEC), necessarily lead to sequence-dependent NTP incorporation rates. Simulated RNAP elongation kinetics is in good agreement with data from transcription gels and single-molecule studies. The model provides a kinetic explanation for well-known back-tracked pauses at transcript positions with unstable TECs. It also predicts a new type of pause caused by an energetically unfavorable transition from pre to post-translocation modes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Pairing
  • Base Sequence
  • Computer Simulation
  • DNA, Bacterial
  • DNA-Directed RNA Polymerases / chemistry*
  • DNA-Directed RNA Polymerases / metabolism*
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Kinetics
  • Models, Biological*
  • Monte Carlo Method
  • Nucleotides / chemistry
  • Nucleotides / metabolism
  • Peptide Chain Elongation, Translational*
  • Templates, Genetic
  • Thermodynamics
  • Transcription, Genetic*

Substances

  • DNA, Bacterial
  • Nucleotides
  • DNA-Directed RNA Polymerases