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arXiv 1102.4576physics.bio-ph
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基因表达随机模型的连接蛋白质和mRNA突发分布

Connecting protein and mRNA burst distributions for stochastic models of gene expression

Vlad Elgart, Tao Jia, Andrew T. Fenley, Rahul V. Kulkarni

摘要:

基因表达的内在随机性可导致遗传相同的细胞的蛋白质水平的较大变异性。这种蛋白质水平的变异性可能是由于mRNA的合成不频繁,这反过来又引起蛋白质表达的爆发。在实验中确实观察到了爆发式蛋白质表达,最近的研究也发现了转录爆发的证据,即爆发式mRNA的产生。考虑到有不同的实验技术来量化基因表达不同阶段的噪音,因此有兴趣导出连接不同水平实验观察的分析结果。在这项工作中,我们考虑随机模型的基因表达的mRNA和蛋白质的生产发生在独立的突发。对于这样的模型,我们推导出连接蛋白质和mRNA的突发分布的分析表达式,这表明如何从蛋白质突发分布中推断mRNA突发分布的功能形式。此外,如果基因表达被抑制,使观察到的蛋白质爆发只出现从单个mRNA,我们展示了如何观察蛋白质爆发分布(抑制和未抑制)可以用来完全确定的mRNA爆发分布。假设独立的贡献,从个人爆发,我们推导出的解析表达式连接的手段和方差的爆发和稳态蛋白质分布。最后,我们验证我们的一般分析结果,考虑一个特定的反应方案,涉及小RNA调控蛋白质爆发。对于一系列的参数,我们推导出的解析表达式的调节蛋白质分布,使用随机模拟验证。因此,在这项工作中获得的分析结果可以作为有用的投入,广泛的研究,重点是在基因表达的随机性。

英文摘要:

The intrinsic stochasticity of gene expression can lead to large variability in protein levels for genetically identical cells. Such variability in protein levels can arise from infrequent synthesis of mRNAs which in turn give rise to bursts of protein expression. Protein expression occurring in bursts has indeed been observed experimentally and recent studies have also found evidence for transcriptional bursting, i.e. production of mRNAs in bursts. Given that there are distinct experimental techniques for quantifying the noise at different stages of gene expression, it is of interest to derive analytical results connecting experimental observations at different levels. In this work, we consider stochastic models of gene expression for which mRNA and protein production occurs in independent bursts. For such models, we derive analytical expressions connecting protein and mRNA burst distributions which show how the functional form of the mRNA burst distribution can be inferred from the protein burst distribution. Additionally, if gene expression is repressed such that observed protein bursts arise only from single mRNAs, we show how observations of protein burst distributions (repressed and unrepressed) can be used to completely determine the mRNA burst distribution. Assuming independent contributions from individual bursts, we derive analytical expressions connecting means and variances for burst and steady-state protein distributions. Finally, we validate our general analytical results by considering a specific reaction scheme involving regulation of protein bursts by small RNAs. For a range of parameters, we derive analytical expressions for regulated protein distributions that are validated using stochastic simulations. The analytical results obtained in this work can thus serve as useful inputs for a broad range of studies focusing on stochasticity in gene expression.

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