EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation and UPF, Dr Aiguader 88, Barcelona, Spain.
Mol Syst Biol. 2011 Jul 19;7:511. doi: 10.1038/msb.2011.38.
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.
细胞内的 DNA、RNA、蛋白质和代谢物之间的复杂相互作用调控着生物功能和细胞对环境干扰的反应。为了在分子水平上理解生命系统中的这些核心过程，我们整合了来自基因组简化细菌支原体的 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了精细的定量分析。对细胞扰动的蛋白质组组成变化揭示了特定的应激反应策略。基因表达的调控在很大程度上与蛋白质动力学脱耦，并且翻译效率对蛋白质丰度的调节作用高于蛋白质周转率。使用体内数据进行的随机模拟表明，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。蛋白质丰度以功能单元（如复合物或途径）进行调节，并反映细胞的生活方式。我们的研究提供了对细胞内平均蛋白质丰度的详细综合分析，以及 mRNA 和蛋白质这两种细胞内中心生物分子的动态相互作用。
