Translational Repression Contributes Greater Noise to Gene Expression than Transcriptional Repression
Translational Repression Contributes Greater Noise to Gene Expression than Transcriptional Repression
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DOI：
10.1016/j.bpj.2008.09.052
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发表时间：
2009-01-21
影响因子：
3.4
通讯作者：
Kierzek, Andrzej M.
中科院分区：
文献类型：
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作者：
Komorowski, Michal;Miekisz, Jacek;Kierzek, Andrzej M.
基因表达的随机效应可能导致单个细胞的不同生理状态，从而影响病原体的生存和人工基因网络的设计。我们从四种基因负表达控制的基本机制中研究了调控因子对基因表达噪声的贡献：1)，蛋白质抑制因子的转录调控，2)，蛋白质的翻译抑制；3) RNA转录抑制；4) RNA对翻译的干扰。我们利用化学主方程和矩生成函数的方法研究了一个双基因网络的一般模型。我们比较了具有相同有效转录和翻译起始率的基因由于不同抑制因子的作用而产生的表达噪声，而以往的研究比较了具有相同平均表达水平但不同起始率的基因的噪声。我们的研究结果表明，翻译抑制比启动子水平的抑制产生更高的噪声，并且这种关系不依赖于定量参数值。我们还表明，蛋白质降解的调节比mRNA的调节降解产生更多的噪声。这些都是出乎意料的结果，因为之前的研究表明，翻译调控更为准确。蛋白质和RNA阻遏物引入的噪声的相对大小取决于蛋白质和mRNA的降解率，并且我们推导了阈值的表达式，低于该阈值，蛋白质阻遏物引入的噪声高于RNA阻遏物引入的噪声。
Stochastic effects in gene expression may result in different physiological states of individual cells, with consequences for pathogen survival and artificial gene network design. We studied the contributions of a regulatory factor to gene expression noise in four basic mechanisms of negative gene expression control: 1), transcriptional regulation by a protein repressor, 2), translational repression by a protein; 3), transcriptional repression by RNA; and 4), RNA interference with the translation. We investigated a general model of a two-gene network, using the chemical master equation and a moment generating function approach. We compared the expression noise of genes with the same effective transcription and translation initiation rates resulting from the action of different repressors, whereas previous studies compared the noise of genes with the same mean expression level but different initiation rates. Our results show that translational repression results in a higher noise than repression on the promoter level, and that this relationship does not depend on quantitative parameter values. We also show that regulation of protein degradation contributes more noise than regulated degradation of mRNA. These are unexpected results, because previous investigations suggested that translational regulation is more accurate. The relative magnitude of the noise introduced by protein and RNA repressors depends on the protein and mRNA degradation rates, and we derived expressions for the threshold below which the noise introduced by a protein repressor is higher than the noise introduced by an RNA repressor.