Degradation rate uniformity determines success of oscillations in repressive feedback regulatory networks

Degradation rate uniformity determines success of oscillations in repressive feedback regulatory networks
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降解率均匀性决定抑制反馈调节网络振荡的成功

DOI:
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发表时间:
2018
影响因子:
3.9
通讯作者:
R. Pérez
R. Pérez
中科院分区:
综合性期刊2区
文献类型:
--
作者:
K. Page;R. Pérez

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环形振荡器是由能够持续振荡的相互作用环组成的生化电路。基因之间的非线性相互作用阻碍了对其功能的分析洞察,通常需要计算探索。在这里,我们表明,尽管明显的复杂性,在一个不相干的反馈环的唯一的稳态的稳定性只取决于退化率和一个单一的参数总结的反馈电路。具体地说,我们表明,产生振荡行为的监管参数的范围是最大化时,降解速率是相等的。引人注目的是,这一结果独立于所使用的调控功能或基因数量。我们还推导出作为退化率和形成环的节点数的函数的振荡的性质。最后,我们探索mRNA动力学的作用,通过将通用结果应用于具有两个自然不同降解时间尺度的特定情况。
Ring oscillators are biochemical circuits consisting of a ring of interactions capable of sustained oscillations. The nonlinear interactions between genes hinder the analytical insight into their function, usually requiring computational exploration. Here, we show that, despite the apparent complexity, the stability of the unique steady state in an incoherent feedback ring depends only on the degradation rates and a single parameter summarizing the feedback of the circuit. Concretely, we show that the range of regulatory parameters that yield oscillatory behaviour is maximized when the degradation rates are equal. Strikingly, this result holds independently of the regulatory functions used or number of genes. We also derive properties of the oscillations as a function of the degradation rates and number of nodes forming the ring. Finally, we explore the role of mRNA dynamics by applying the generic results to the specific case with two naturally different degradation timescales.
DOI: 10.1126/science.3018930
发表时间: 1986-10-10
期刊: SCIENCE
影响因子: 56.9
作者:
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