Sequence-dependent kinetic model for transcription elongation by RNA polymerase.
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.
Bai
Lu
L
Department of Physics, Laboratory of Atomic and Solid State Physics, Cornell University, Ithaca, NY 14853, USA.
Shundrovsky
Alla
A
Wang
Michelle D
MD
D020029:Base Pairing; D001483:Base Sequence; D003198:Computer Simulation; D004269:DNA, Bacterial; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry* / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D007700:Kinetics; D008954:Models, Biological; D009010:Monte Carlo Method; D009711:Nucleotides / Q000737:chemistry / Q000378:metabolism; D010441:Peptide Chain Elongation, Translational; D013698:Templates, Genetic; D013816:Thermodynamics; D014158:Transcription, Genetic
D004269:DNA, Bacterial; D009711:Nucleotides; D012321:DNA-Directed RNA Polymerases