Aquino Tomás, Abranches Elsa, Nunes Ana
Centro de Física da Matéria Condensada and Departamento de Física, Faculdade de Ciências da Universidade de Lisboa, P-1649-003 Lisboa, Portugal.
Phys Rev E Stat Nonlin Soft Matter Phys. 2012 Jun;85(6 Pt 1):061913. doi: 10.1103/PhysRevE.85.061913. Epub 2012 Jun 19.
A detailed stochastic model of single-gene autoregulation is established and its solutions are explored when mRNA dynamics is fast compared with protein dynamics and in the opposite regime. The model includes all the sources of randomness that are intrinsic to the autoregulation process and it considers both transcriptional and post-transcriptional regulation. The time-scale separation allows the derivation of analytic expressions for the equilibrium distributions of protein and mRNA. These distributions are generally well described in the continuous approximation, which is used to discuss the qualitative features of the protein equilibrium distributions as a function of the biological parameters in the fast mRNA regime. The performance of the time-scale approximation is assessed by comparison with simulations of the full stochastic system, and a good quantitative agreement is found for a wide range of parameter values. We show that either unimodal or bimodal equilibrium protein distributions can arise, and we discuss the autoregulation mechanisms associated with bimodality.
建立了单基因自调控的详细随机模型,并在mRNA动力学比蛋白质动力学快以及相反情况下探讨其解。该模型包括自调控过程固有的所有随机源,并同时考虑转录和转录后调控。时间尺度分离允许推导蛋白质和mRNA平衡分布的解析表达式。这些分布通常在连续近似中得到很好的描述,该近似用于讨论快速mRNA状态下蛋白质平衡分布作为生物学参数函数的定性特征。通过与完整随机系统的模拟进行比较来评估时间尺度近似的性能,并且在广泛的参数值范围内发现了良好的定量一致性。我们表明可以出现单峰或双峰平衡蛋白质分布,并讨论与双峰性相关的自调控机制。