Wang Xia, Li Yan, Xu Xue, Wang Yong-hua
Center of Bioinformatics, Northwest A&F University, Yangling, Shaanxi, China.
Biosystems. 2010 Apr;100(1):31-8. doi: 10.1016/j.biosystems.2009.12.005. Epub 2009 Dec 28.
The microRNA (miRNA) pathway plays multiple roles in regulating mechanisms controlling both physiological and pathological processes such as the cell proliferation and cancers. But little is known about the dynamic properties, key rate-limiting steps as well as the stochastic noise in this pathway. Presently, a system-theoretic approach was presented to analyze and quantitative modeling of a generic miRNA pathway, which can be implemented deterministically and stochastically. Our results show that the inferred dynamic properties obtained from the mathematical models of the miRNA pathway are well consistent with previous experimental observations. By sensitivity analysis, the key steps in this pathway were found to be the miRNA gene transcription, RISC decay and mRNA formation. In addition, the results of quantified noise strength along the pathway demonstrate that the pathway can reduce the ingress noise and reveal the noise robustness property. Our findings also present testable hypothesis for experimental biologists to further investigate miRNA's increasing functional roles in regulating various cellular processes.
微小RNA（miRNA）途径在调控生理和病理过程（如细胞增殖和癌症）的机制中发挥着多种作用。但对于该途径的动态特性、关键限速步骤以及随机噪声，我们却知之甚少。目前，我们提出了一种系统理论方法，用于对通用miRNA途径进行分析和定量建模，该方法可以确定性地和随机地实现。我们的结果表明，从miRNA途径的数学模型中推断出的动态特性与先前的实验观察结果高度一致。通过敏感性分析，发现该途径中的关键步骤是miRNA基因转录、RNA诱导沉默复合体（RISC）降解和信使核糖核酸（mRNA）形成。此外，沿该途径的量化噪声强度结果表明，该途径可以降低进入噪声并揭示噪声稳健性特性。我们的研究结果还为实验生物学家提供了可检验的假设，以便进一步研究miRNA在调节各种细胞过程中日益增加的功能作用。
