Abstract
Several key transcription factors have unusually short half-lives compared to other cellular proteins. Here, we explore the utility of active degradation in shaping how the multiple antibiotic resistance activator MarA coordinates its downstream targets. MarA controls a variety of stress response genes in Escherichia coli. We modify its half-life either by knocking down the protease that targets it via CRISPRi or by engineering MarA to protect it from degradation. Our experimental and analytical results indicate that active degradation can impact both the rate of coordination and the maximum coordination that downstream genes can achieve. In the context of multi-gene regulation, trade-offs between these properties show that perfect information fidelity and instantaneous coordination cannot coexist.
Highlights
Active degradation is a rare feature in bacteria, affecting only 2–7% of total cellular proteins in Escherichia coli [1,2]
We focused on the multi-antibiotic resistance activator (MarA) in E. coli as a case study
We first developed an analytic model of how noise in MarA propagates to downstream genes as a function of its half-life to generate predictions that we could test experimentally
Summary
Active degradation is a rare feature in bacteria, affecting only 2–7% of total cellular proteins in Escherichia coli [1,2]. Active degradation is accomplished by ATP-dependent proteases such as ClpXP, HflB, and Lon [3]. These proteases play a role in protein quality control by degrading. Active degradation of MarA controls downstream coordination
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