Roussel Marc R, Zhu Rui
Department of Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Alberta T1K 3M4, Canada.
Bull Math Biol. 2006 Oct;68(7):1681-713. doi: 10.1007/s11538-005-9048-6. Epub 2006 Jun 20.
We study a stochastic model of transcription kinetics in order to characterize the distributions of transcriptional delay and of elongation rates. Transcriptional delay is the time which elapses between the binding of RNA polymerase to a promoter sequence and its dissociation from the DNA template strand with consequent release of the transcript. Transcription elongation is the process by which the RNA polymerase slides along the template strand. The model considers a DNA template strand with one promoter site and n nucleotide sites, and five types of reaction processes, which we think are key ones in transcription. The chemical master equation is a set of ordinary differential equations in 3(n) variables, where n is the number of bases in the template. This model is too huge to be handled if n is large. We manage to get a reduced Markov model which has only 2n independent variables and can well approximate the original dynamics. We obtain a number of analytical and numerical results for this model, including delay and transcript elongation rate distributions. Recent studies of single-RNA polymerase transcription by using optical-trapping techniques raise an issue of whether the elongation rates measured in a population are heterogeneous or not. Our model implies that in the cases studied, different RNA polymerase molecules move at different characteristic rates along the template strand. We also discuss the implications of this work for the mathematical modeling of genetic regulatory circuits.
我们研究转录动力学的随机模型,以表征转录延迟和延伸速率的分布。转录延迟是指RNA聚合酶与启动子序列结合到其从DNA模板链解离并随之释放转录本之间所经过的时间。转录延伸是RNA聚合酶沿着模板链滑动的过程。该模型考虑了具有一个启动子位点和n个核苷酸位点的DNA模板链,以及五种反应过程,我们认为这些是转录中的关键过程。化学主方程是一组包含3(n)个变量的常微分方程,其中n是模板中的碱基数。如果n很大,这个模型就会太大而难以处理。我们设法得到了一个简化的马尔可夫模型,它只有2n个独立变量,并且能够很好地近似原始动力学。我们为这个模型获得了许多解析和数值结果,包括延迟和转录本延伸速率分布。最近利用光镊技术对单RNA聚合酶转录的研究提出了一个问题,即在群体中测量的延伸速率是否存在异质性。我们的模型表明,在所研究的情况下,不同的RNA聚合酶分子沿着模板链以不同的特征速率移动。我们还讨论了这项工作对基因调控回路数学建模的意义。