Homeostasis of protein and mRNA concentrations in growing cells.
Homeostasis of protein and mRNA concentrations in growing cells.
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DOI：
10.1038/s41467-018-06714-z
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发表时间：
2018-10-29
影响因子：
16.6
通讯作者：
Amir A
中科院分区：
文献类型：
--
作者：
Lin J;Amir A
许多实验表明，在生长的细胞中，mRNA和蛋白质的数量与细胞体积成正比。然而，随机基因表达的模型通常假设每个基因的恒定转录速率和每个mRNA的恒定翻译速率，这与这些实验不相容。在这里，我们构建了一个最小的基因表达模型来填补这一空白。假设核糖体和RNA聚合酶限制基因表达，我们表明，蛋白质和mRNA的数量都在细胞周期中呈指数增长，所有mRNA和蛋白质的浓度实现细胞内稳态; RNA聚合酶的基因之间的竞争使得转录速率独立于基因组数量。此外，通过将模型扩展到DNA（mRNA）可以被RNA聚合酶（核糖体）饱和并变得受限的情况，我们预测随着蛋白质与DNA比率的增加，细胞体积从指数增长过渡到线性增长。对于各种生物体，mRNA和蛋白质拷贝数与细胞体积成比例。在这里，作者表明，当核糖体和RNAP限制表达时，这一结果自然出现。此外，作者表明，在他们的模型中，这一结果在足够高的体积/DNA比下被打破。
Many experiments show that the numbers of mRNA and protein are proportional to the cell volume in growing cells. However, models of stochastic gene expression often assume constant transcription rate per gene and constant translation rate per mRNA, which are incompatible with these experiments. Here, we construct a minimal gene expression model to fill this gap. Assuming ribosomes and RNA polymerases are limiting in gene expression, we show that the numbers of proteins and mRNAs both grow exponentially during the cell cycle and that the concentrations of all mRNAs and proteins achieve cellular homeostasis; the competition between genes for the RNA polymerases makes the transcription rate independent of the genome number. Furthermore, by extending the model to situations in which DNA (mRNA) can be saturated by RNA polymerases (ribosomes) and becomes limiting, we predict a transition from exponential to linear growth of cell volume as the protein-to-DNA ratio increases. For various organisms, mRNA and protein copy numbers scale with cell volume. Here, the authors show that this result emerges naturally when ribosomes and RNAPs limit expression. Furthermore, the authors show that within their model this result breaks down for a sufficiently high volume/DNA ratio.
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影响因子：
48
作者：
Godin, Michel;Delgado, Francisco Feijo;Son, Sungmin;Grover, William H.;Bryan, Andrea K.;Tzur, Amit;Jorgensen, Paul;Payer, Kris;Grossman, Alan D.;Kirschner, Marc W.;Manalis, Scott R.
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影响因子：
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影响因子：
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影响因子：
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作者：
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通讯作者：
Cooper, Stephen
影响因子：
4.6
作者：
Ghusinga KR;Vargas-Garcia CA;Singh A
通讯作者：
Singh A