Martin Benjamin, Suter David M
Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
iScience. 2023 Aug 28;26(10):107758. doi: 10.1016/j.isci.2023.107758. eCollection 2023 Oct 20.
The level of a given protein is determined by the synthesis and degradation rates of its mRNA and protein. While several studies have quantified the contribution of different gene expression steps in regulating protein levels, these are limited by using equilibrium approximations in out-of-equilibrium biological systems. Here, we introduce gene expression flux analysis to quantitatively dissect the dynamics of the expression level for specific proteins and use it to analyze published transcriptomics and proteomics datasets. Our analysis reveals distinct regulatory modalities shared by sets of genes with clear functional signatures. We also find that protein degradation plays a stronger role than expected in the adaptation of protein levels. These findings suggest that shared regulatory strategies can lead to versatile responses at the protein level and highlight the importance of going beyond equilibrium approximations to dissect the quantitative contribution of different steps of gene expression to protein dynamics.
给定蛋白质的水平由其mRNA和蛋白质的合成与降解速率决定。虽然有几项研究对不同基因表达步骤在调节蛋白质水平中的作用进行了量化,但这些研究因在非平衡生物系统中使用平衡近似而受到限制。在此,我们引入基因表达通量分析来定量剖析特定蛋白质表达水平的动态变化,并利用它来分析已发表的转录组学和蛋白质组学数据集。我们的分析揭示了具有明确功能特征的基因集所共有的独特调控模式。我们还发现,蛋白质降解在蛋白质水平的适应性变化中所起的作用比预期的更强。这些发现表明,共享的调控策略可导致蛋白质水平上的多样反应,并突出了超越平衡近似以剖析基因表达不同步骤对蛋白质动态变化的定量贡献的重要性。