Global quantification of mammalian gene expression control
Global quantification of mammalian gene expression control
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DOI：
10.1038/nature10098
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发表时间：
2011-05-19
期刊：
影响因子：
64.8
通讯作者：
Selbach, Matthias
中科院分区：
文献类型：
--
作者：
Schwanhaeusser, Bjoern;Busse, Dorothea;Selbach, Matthias
基因表达是一个多步骤的过程，涉及信使RNA和蛋白质的转录、翻译和周转。虽然它是生命最基本的过程之一，但整个级联从未在全基因组范围内量化。在这里，我们同时测量绝对mRNA和蛋白质丰度和营业额的平行代谢脉冲标记的哺乳动物细胞中的5,000多个基因。虽然mRNA和蛋白质水平的相关性比以前认为的要好，但相应的半衰期没有显示出相关性。使用定量模型，我们已经获得了第一个基因组规模的预测的mRNA和蛋白质的合成速率。我们发现，蛋白质的细胞丰度主要控制在翻译水平。具有类似mRNA和蛋白质稳定性组合的基因具有共同的功能特性，表明半衰期是在能量和动态约束下演变的。关于基因表达各个阶段的定量信息提供了丰富的资源，有助于更好地理解潜在的设计原则。
Gene expression is a multistep process that involves the transcription, translation and turnover of messenger RNAs and proteins. Although it is one of the most fundamental processes of life, the entire cascade has never been quantified on a genome-wide scale. Here we simultaneously measured absolute mRNA and protein abundance and turnover by parallel metabolic pulse labelling for more than 5,000 genes in mammalian cells. Whereas mRNA and protein levels correlated better than previously thought, corresponding half-lives showed no correlation. Using a quantitative model we have obtained the first genome-scale prediction of synthesis rates of mRNAs and proteins. We find that the cellular abundance of proteins is predominantly controlled at the level of translation. Genes with similar combinations of mRNA and protein stability shared functional properties, indicating that half-lives evolved under energetic and dynamic constraints. Quantitative information about all stages of gene expression provides a rich resource and helps to provide a greater understanding of the underlying design principles.