Department of Applied Physics, Chalmers University of Technology, S-412 96 Göteborg, Sweden.
Chaos. 2011 Jun;21(2):023135. doi: 10.1063/1.3605464.
The experiments indicate that the transcription of genes into ncRNA can positively or negatively interfere with transcription into mRNA. We propose two kinetic models describing this effect. The first model is focused on the ncRNA-induced chromatin modification facilitating the transcription of the downstream gene into mRNA. The second model includes the competition between the transcription into ncRNA and the binding of activator to a regulatory site of the downstream gene transcribed into mRNA. Our analysis based on the mean-field kinetic equations and Monte Carlo simulations shows the likely dependences of the transcription rate on RNA polymerase concentration in situations with different rate-limiting steps. Our models can also be used to scrutinize the dependence of the transcription rate on other kinetic parameters. Our kinetic Monte Carlo simulations show that the first model predicts stochastic bursts in the mRNA formation provided that the transcription into ncRNA is slow, while the second model predicts in addition anti-phase stochastic bursts in the mRNA and ncRNA formation provided that that the protein attachment to and detachment from a regulatory site is slow.
实验表明,基因转录为 ncRNA 可以正向或负向干扰转录为 mRNA。我们提出了两个描述这种效应的动力学模型。第一个模型侧重于 ncRNA 诱导的染色质修饰,促进下游基因转录为 mRNA。第二个模型包括 ncRNA 转录和激活剂与下游基因转录为 mRNA 的调控位点结合之间的竞争。我们基于平均场动力学方程和蒙特卡罗模拟的分析表明,在具有不同限速步骤的情况下,转录酶浓度可能对转录速率有依赖性。我们的模型还可以用于仔细研究转录速率对其他动力学参数的依赖性。我们的动力学蒙特卡罗模拟表明,第一个模型预测了 mRNA 形成的随机爆发,前提是 ncRNA 的转录速度较慢,而第二个模型则预测了 mRNA 和 ncRNA 形成的反相随机爆发,前提是蛋白质与调控位点的附着和脱附速度较慢。