Quantification of mRNA and protein and integration with protein turnover in a bacterium.
Quantification of mRNA and protein and integration with protein turnover in a bacterium.
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DOI：
10.1038/msb.2011.38
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发表时间：
2011-07-19
影响因子：
9.9
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在不同生长条件下测定400种蛋白质的平均细胞拷贝数，并结合蛋白质周转率和绝对mRNA水平，揭示了基因组减少的细菌肺炎支原体中蛋白质表达的动态。生物功能和细胞对环境扰动的反应受到细胞内DNA、RNA、蛋白质和代谢物复杂相互作用的调节。为了在分子水平上理解生命系统中的这些中心过程，我们整合了基因组减少的细菌肺炎支原体的mRNA、蛋白质以及单个蛋白质半衰期的实验测定丰度数据。我们对各种外部条件下的基本细胞内过程进行细粒度的定量分析。蛋白质组组成的变化，响应细胞扰动揭示了特定的应激反应策略。基因表达的调节在很大程度上与蛋白质动力学脱钩，并且翻译效率对蛋白质丰度的调节影响高于蛋白质周转。使用体内数据的随机模拟显示了低翻译效率和长蛋白质半衰期如何有效地降低基因表达中的生物噪声。蛋白质丰度在功能单位中受到调节，如复合物或途径，并反映细胞的生活方式。我们的研究提供了一个详细的综合分析平均细胞蛋白质丰度和mRNA和蛋白质，细胞的中心生物分子的动态相互作用。
Determination of the average cellular copy number of 400 proteins under different growth conditions and integration with protein turnover and absolute mRNA levels reveals the dynamics of protein expression in the genome-reduced bacterium Mycoplasma pneumoniae. Biological function and cellular responses to environmental perturbations are regulated by a complex interplay of DNA, RNA, proteins and metabolites inside cells. To understand these central processes in living systems at the molecular level, we integrated experimentally determined abundance data for mRNA, proteins, as well as individual protein half-lives from the genome-reduced bacterium Mycoplasma pneumoniae. We provide a fine-grained, quantitative analysis of basic intracellular processes under various external conditions. Proteome composition changes in response to cellular perturbations reveal specific stress response strategies. The regulation of gene expression is largely decoupled from protein dynamics and translation efficiency has a higher regulatory impact on protein abundance than protein turnover. Stochastic simulations using in vivo data show how low translation efficiency and long protein half-lives effectively reduce biological noise in gene expression. Protein abundances are regulated in functional units, such as complexes or pathways, and reflect cellular lifestyles. Our study provides a detailed integrative analysis of average cellular protein abundances and the dynamic interplay of mRNA and proteins, the central biomolecules of a cell.