A look-ahead model for the elongation dynamics of transcription.
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.
Yamada
Yujiro Richard
YR
Department of Mathematics, University of Michigan, Ann Arbor, Michigan, USA.
Peskin
Charles S
CS
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
D012265:Ribonucleotides; D012313:RNA; D004247:DNA; D012321:DNA-Directed RNA Polymerases