Direct comparison of small RNA and transcription factor signaling.

Direct comparison of small RNA and transcription factor signaling.
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DOI:
10.1093/nar/gks439
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发表时间:
2012-08
影响因子:
14.9
通讯作者:
Lim HN
Lim HN
中科院分区:
生物学2区
文献类型:
--
作者:
Hussein R;Lim HN

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小RNA(sRNA)和充当转录因子(TF)的蛋白质是基因网络的主要组成部分。这两类信号分子具有不同的作用机制; sRNA控制mRNA翻译,而TF控制mRNA转录。在这里,我们直接比较sRNA和TF信号的性质,使用数学模型和大肠杆菌中的合成基因电路。我们展示了sRNA作用于现有靶mRNA的能力(与TF相反,TF会改变未来靶mRNA的产生),并且在不需要首先翻译的情况下,对动态的影响令人惊讶地很小。相反,动力学主要由sRNA和TF的清除率、稳态浓度和响应曲线决定;这些因素决定了靶基因表达能够最大限度地响应sRNA和TF转录变化之前的时间延迟。这些发现广泛适用于基因网络中信号的分析,我们证明它们可以用于合理地重新编程合成电路的动态。
Small RNAs (sRNAs) and proteins acting as transcription factors (TFs) are the principal components of gene networks. These two classes of signaling molecules have distinct mechanisms of action; sRNAs control mRNA translation, whereas TFs control mRNA transcription. Here, we directly compare the properties of sRNA and TF signaling using mathematical models and synthetic gene circuits in Escherichia coli. We show the abilities of sRNAs to act on existing target mRNAs (as opposed to TFs, which alter the production of future target mRNAs) and, without needing to be first translated, have surprisingly little impact on the dynamics. Instead, the dynamics are primarily determined by the clearance rates, steady-state concentrations and response curves of the sRNAs and TFs; these factors determine the time delay before a target gene’s expression can maximally respond to changes in sRNA and TF transcription. The findings are broadly applicable to the analysis of signaling in gene networks, and we demonstrate that they can be used to rationally reprogram the dynamics of synthetic circuits.
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