Flux Analysis Reveals Specific Regulatory Modalities of Gene Expression

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.