Theoretical Analysis of Catalytic-sRNA-Mediated Gene Silencing
Theoretical Analysis of Catalytic-sRNA-Mediated Gene Silencing
复制标题
DOI：
10.1016/j.jmb.2010.12.008
复制
发表时间：
2011-02-11
影响因子：
5.6
通讯作者：
Shi, Hualin
中科院分区：
文献类型：
--
作者：
Hao, Yue;Xu, Liufang;Shi, Hualin
小调控RNA（small regulatory RNA，sRNA）是一种通过反义机制发挥作用的RNA，在转录后水平上对基因调控起着关键作用。最近，一种与外膜蛋白调控相关的Hfq依赖性sRNA MicM由于其催化调控模式而被证实为一种新的反义sRNA。在这里，我们提出了一个简单的动力学模型的酶样调节模式的sRNA和详细研究的噪声特性下的调节器的各种回收率的目标基因。我们预测sRNA的回收率和其他相关参数对目标表达的噪声强度有显著影响。与化学计量调控模式相比，在sRNA和靶mRNA的转录速率相等的阈值附近观察到靶表达的较小波动。我们还发现，新模式在对外部信号的快速响应方面更好。然而，如果刺激信号消失，则需要更多的时间来实现目标恢复。此外，基于该模型得到的MicM-ybfM相互作用体系的时间演化结果与以往的实验结果一致，为理论分析提供了实验依据. (C)2010爱思唯尔有限公司版权所有。
Small regulatory RNA (sRNA) that acts by an antisense mechanism is critical for gene regulation at the posttranscriptional level. Recently, an Hfq-dependent sRNA named MicM, which is related to the regulation of outer membrane protein, was verified as a novel antisense sRNA due to its catalytic mode of regulation. Here we propose a simple kinetic model for the enzyme-like regulation mode of sRNA and study in detail the noise properties of the target gene under various recycling rates of the regulator. We predict that the recycling rate of sRNA and other relative parameters have significant influence on the noise strength of target expression. In comparison with the stoichiometric regulatory mode, a lesser fluctuation of target expression was observed near the threshold at which the transcription rates of both sRNA and target mRNA equal each other. We also found that the new mode is better in terms of rapid response to external signals. However, it needs more time to achieve target recovery if the stimulating signal disappears. Additionally, the obtained time evolution results of the MicM-ybfM interaction system based on our model are consistent with previous experimental results, serving as experimental evidence to back up our theoretical analysis. (C) 2010 Elsevier Ltd. All rights reserved.