Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, D-13092 Berlin, Germany.
Nature. 2011 May 19;473(7347):337-42. doi: 10.1038/nature10098.
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.
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。尽管这是生命最基本的过程之一，但整个级联反应从未在全基因组范围内进行过定量。在这里，我们通过对哺乳动物细胞中超过 5000 个基因进行平行代谢脉冲标记，同时测量了 mRNA 和蛋白质的绝对丰度和周转。尽管 mRNA 和蛋白质水平的相关性比之前认为的要好，但相应的半衰期却没有相关性。使用一个定量模型，我们首次对 mRNA 和蛋白质的合成速率进行了全基因组预测。我们发现，蛋白质的细胞丰度主要在翻译水平上受到控制。具有相似 mRNA 和蛋白质稳定性组合的基因具有相似的功能特性，这表明半衰期是在能量和动态限制下进化而来的。关于基因表达所有阶段的定量信息提供了丰富的资源，并有助于更好地理解潜在的设计原则。
