Motion of RNA Polymerase along DNA: A Stochastic Model

• Published in: Biophysical journal 1998-03, Vol.74 (3), p.1169-1185
• Main Authors: Jülicher, Frank, Bruinsma, Robijn
• Format: Article
• Language: English
• Subjects: Base Sequence; DNA - chemistry; DNA - metabolism; DNA-Directed RNA Polymerases - chemistry; DNA-Directed RNA Polymerases - metabolism; Kinetics; Markov Chains; Models, Chemical; Models, Molecular; Molecular Sequence Data; Nucleic Acid Conformation; RNA - biosynthesis; RNA - chemistry; Stochastic Processes; Transcription, Genetic
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/S0006-3495(98)77833-6

RNA polymerase is a key transcription enzyme that moves along a DNA double helix to polymerize an RNA transcript. Recent progress in micromechanical experiments permits quantitative studies of forces and motion generated by the enzyme. We present in this paper a chemical kinetics description of RNA polymerase motion. The model is based on a classical chemical kinetics description of polymerization reactions driven by a free energy gain that depends on forces applied externally at the catalytic site. The RNA polymerase controlled activation barrier of the reaction is assumed to be strongly dependent on inhibitory internal strains of the RNA polymerase molecule. The sequence sensitivity of RNA polymerase is described by a linear coupling between the height of the activation barrier and the local DNA sequence. Our model can simulate optical trap experiments and allows us to study the dynamics of chemically halted complexes that are important for footprinting studies. We find that the effective stall force is a sequence-dependent, statistical quantity, whose distribution depends on the observation time. The results are consistent with the experimental observations to date.