Frequency modulation of stochastic gene expression bursts by strongly interacting small RNAs
Frequency modulation of stochastic gene expression bursts by strongly interacting small RNAs
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强相互作用小RNA对随机基因表达爆发的频率调节
DOI：
10.1103/physreve.94.042419
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发表时间：
2016
影响因子：
2.4
通讯作者：
Kulkarni Rahul V
中科院分区：
文献类型：
--
作者：
Kumar Niraj;Jia Tao;Zarringhalam Kourosh;Kulkarni Rahul V
基因表达在单细胞水平上的偶发性质——长时间的不活动被mRNA或蛋白质产生的爆发打断——在多种细胞过程中起着关键作用。为了阐明爆发在基因表达中的细胞作用，合成生物学方法已被用于设计具有爆发mRNA或蛋白质生产的简单遗传回路。要理解如何设计这样的基因回路，使其具有控制爆发相关参数的能力，需要开发基因表达的定量随机模型。在这项工作中，我们分析了通过强相互作用的小rna调控基因表达爆发的随机模型。对于所考虑的参数范围，基于平均场方法的结果明显不准确，需要替代的分析方法。通过简化近似，我们得到了与随机模拟结果一致的稳态分布的解析结果。这些结果表明，在强相互作用的限制下，小rna的调控可以有效地调节破裂的频率。我们探讨了这种涉及反馈效应和启动子状态之间切换的简单遗传回路的调节的后果。
The sporadic nature of gene expression at the single-cell level—long periods of inactivity punctuated by bursts of mRNA or protein production—plays a critical role in diverse cellular processes. To elucidate the cellular role of bursting in gene expression, synthetic biology approaches have been used to design simple genetic circuits with bursty mRNA or protein production. Understanding how such genetic circuits can be designed with the ability to control burst-related parameters requires the development of quantitative stochastic models of gene expression. In this work, we analyze stochastic models for the regulation of gene expression bursts by strongly interacting small RNAs. For the parameter range considered, results based on mean-field approaches are significantly inaccurate and alternative analytical approaches are needed. Using simplifying approximations, we obtain analytical results for the corresponding steady-state distributions that are in agreement with results from stochastic simulations. These results indicate that regulation by small RNAs, in the strong interaction limit, can be used to effectively modulate the frequency of bursting. We explore the consequences of such regulation for simple genetic circuits involving feedback effects and switching between promoter states.