title: A look-ahead model for the elongation dynamics of transcription.
abstract: This article introduces a chemical kinetic model of the transcriptional elongation dynamics of RNA polymerase. The model's novel concept is a look-ahead feature, in which nucleotides bind reversibly to the DNA before being incorporated covalently into the nascent RNA chain. Analytical and computational methods for studying the behavior of the look-ahead model are introduced, and several approaches to parameter estimation are tested on synthetic and also on actual experimental data. Two types of experimental data are considered: 1), the mean velocity of RNA polymerase as a function of the ambient concentrations of the ribonucleoside triphosphates; and 2), the distribution of time intervals between the forward steps of RNA polymerase. By separately fitting the look-ahead model to these two types of data, we obtain estimates of the model parameters. The most difficult parameter to estimate is the width of the look-ahead window. Both types of data suggest a small window size, but the second type does a better job of distinguishing the different window sizes. These latter data rule out a window size of 1, and they strongly suggest a look-ahead window that is approximately four bases in width. Additional experiments to determine the window size are proposed.
authors.affiliation: Department of Mathematics, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Yujiro Richard
authors.initials: YR
authors.lastname: Yamada
authors.forename: Charles S
authors.initials: CS
authors.lastname: Peskin
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D004247:DNA / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism*; D007700:Kinetics; D008957:Models, Genetic; D011336:Probability; D012313:RNA / Q000096:biosynthesis*; D012265:Ribonucleotides / Q000378:metabolism; D013269:Stochastic Processes; D014158:Transcription, Genetic
chemical_list: D012265:Ribonucleotides; D012313:RNA; D004247:DNA; D012321:DNA-Directed RNA Polymerases