Exploring the effect of network topology, mRNA and protein dynamics on gene regulatory network stability

Homeostasis of protein concentrations in cells is crucial for their proper functioning, requiring steady-state concentrations to be stable to fluctuations. Since gene expression is regulated by proteins such as transcription factors (TFs), the full set of proteins within the cell constitutes a large system of interacting components, which can become unstable. We explore factors affecting stability by coupling the dynamics of mRNAs and proteins in a growing cell. We find that mRNA degradation rate does not affect stability, contrary to previous claims. However, global structural features of the network can dramatically enhance stability. Importantly, a network resembling a bipartite graph with a lower fraction of interactions that target TFs has a higher chance of being stable. Scrambling the E. coli transcription network, we find that the biological network is significantly more stable than its randomized counterpart, suggesting that stability constraints may have shaped network structure during the course of evolution. Maintaining protein expression levels is essential to cellular homeostasis. Here, the authors investigate how transcription factors affect the stability of protein expression in a gene regulatory network, and highlight the importance of network topology.

Automated summary

Maintaining stable protein concentrations in cells is crucial for proper cellular functioning, with network topology playing a key role in ensuring stability constraints and shaping evolutionary processes.