Nonmodular oscillator and switch based on RNA decay drive regeneration of multimodal gene expression.
Nonmodular oscillator and switch based on RNA decay drive regeneration of multimodal gene expression.
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基于RNA衰变的非模块化振荡器和开关驱动多模态基因表达的再生 。
DOI：
10.1093/nar/gkac217
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发表时间：
2022-04-22
影响因子：
14.9
通讯作者：
Hong, Tian
中科院分区：
文献类型：
--
作者：
Nordick, Benjamin;Yu, Polly Y.;Liao, Guangyuan;Hong, Tian
周期性基因表达动态是细胞和生物体生理学的关键。振荡表达的研究主要集中在具有直观调节负反馈回路的网络上，尚不清楚其他常见的生化反应是否也会产生振荡。振荡和噪声已被提出支持哺乳动物祖细胞从极端亚群中恢复异质、多模态表达的能力，但潜在的网络和噪声的具体作用仍然难以捉摸。我们使用基于质量作用的模型来表明，涉及两种RNA的调节RNA降解（适用于近一半的人类蛋白质编码基因）可以在没有明确反馈的情况下产生持续的振荡。发散振荡周期与噪声协同作用，在天的时间尺度上稳健地恢复细胞群体的双峰表达。组织这种发散的全局分岔依赖于一个振荡器和双稳态开关，而双稳态开关不能分解为两个结构模块。我们的工作揭示了转录后反应的丰富动态，以及潜在的广泛机制，包括发育、组织再生和癌细胞异质性。以rna为中心的反应网络在没有明确反馈的情况下，通过顺序结合和协同衰变产生振荡和双稳性。振荡具有不同的周期，它可以与噪声协同，以支持在天的时间尺度上细胞群体中多模态基因表达的稳健恢复。
Periodic gene expression dynamics are key to cell and organism physiology. Studies of oscillatory expression have focused on networks with intuitive regulatory negative feedback loops, leaving unknown whether other common biochemical reactions can produce oscillations. Oscillation and noise have been proposed to support mammalian progenitor cells’ capacity to restore heterogenous, multimodal expression from extreme subpopulations, but underlying networks and specific roles of noise remained elusive. We use mass-action-based models to show that regulated RNA degradation involving as few as two RNA species—applicable to nearly half of human protein-coding genes—can generate sustained oscillations without explicit feedback. Diverging oscillation periods synergize with noise to robustly restore cell populations’ bimodal expression on timescales of days. The global bifurcation organizing this divergence relies on an oscillator and bistable switch which cannot be decomposed into two structural modules. Our work reveals surprisingly rich dynamics of post-transcriptional reactions and a potentially widespread mechanism underlying development, tissue regeneration, and cancer cell heterogeneity. An RNA-centric reaction network generates oscillation and bistability via sequential binding and cooperative decay without explicit feedback. The oscillation has diverging periods and it can synergize with noise to support robust recovery of multimodal gene expression in a cell population on timescales of days.
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DOI：
10.1016/j.biosystems.2018.07.006
发表时间：
2018-09
期刊：
Bio Systems
影响因子：
--
作者：
Choi K;Medley JK;König M;Stocking K;Smith L;Gu S;Sauro HM
通讯作者：
Sauro HM
影响因子：
2.9
作者：
Ermentrout, B
通讯作者：
Ermentrout, B
影响因子：
64.8
作者：
Chang, Hannah H.;Hemberg, Martin;Huang, Sui
通讯作者：
Huang, Sui
影响因子：
4.6
作者：
Abranches, Elsa;Guedes, Ana M. V.;Henrique, Domingos
通讯作者：
Henrique, Domingos
影响因子：
9.2
作者：
Baccarini, Alessia;Chauhan, Hemangini;Gardner, Thomas J.;Jayaprakash, Anitha D.;Sachidanandam, Ravi;Brown, Brian D.
通讯作者：
Brown, Brian D.