sRNA-regulated质粒维持模型
Modeling sRNA-regulated Plasmid Maintenance
摘要：
我们研究了细菌中质粒维持的毒素-抗毒素（HOK/SOK）机制的理论模型。毒素-抗毒素系统通过分离后杀死已丢失质粒的细胞来维持质粒。其功能的关键是通过sRNA抗毒素严格调节蛋白质毒素的表达。在这里，我们专注于毒素-抗毒素机制的调节回路动力学的非线性性质。该机制依赖于蛋白质浓度的瞬时增加，而不是遗传电路的稳定状态。通过系统的分析，这种瞬时增加的参数依赖性，我们确认了一些已知的设计特点，这个系统，并确定新的：一个有效的毒素-抗毒素机制，毒素的mRNA模板的合成速率应低于sRNA抗毒素，mRNA模板应比sRNA抗毒素更稳定，和mRNA-sRNA复合物应比sRNA抗毒素更稳定。此外，蛋白质毒素的短半衰期也有利于毒素-抗毒素系统的功能。此外，我们研究了一种治疗方案，其中引入竞争者mRNA以隔离sRNA抗毒素，从而导致有毒蛋白的表达。
英文摘要：
We study a theoretical model for the toxin-antitoxin (hok/sok) mechanism for plasmid maintenance in bacteria. Toxin-antitoxin systems enforce the maintenance of a plasmid through post-segregational killing of cells that have lost the plasmid. Key to their function is the tight regulation of expression of a protein toxin by an sRNA antitoxin. Here, we focus on the nonlinear nature of the regulatory circuit dynamics of the toxin-antitoxin mechanism. The mechanism relies on a transient increase in protein concentration rather than on the steady state of the genetic circuit. Through a systematic analysis of the parameter dependence of this transient increase, we confirm some known design features of this system and identify new ones: for an efficient toxin-antitoxin mechanism, the synthesis rate of the toxin's mRNA template should be lower that of the sRNA antitoxin, the mRNA template should be more stable than the sRNA antitoxin, and the mRNA-sRNA complex should be more stable than the sRNA antitoxin. Moreover, a short half-life of the protein toxin is also beneficial to the function of the toxin-antitoxin system. In addition, we study a therapeutic scenario in which a competitor mRNA is introduced to sequester the sRNA antitoxin, causing the toxic protein to be expressed.
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