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Liquid–liquid phase separation driven compartmentalization of reactive nucleoplasm
Physical Biology ( IF 2.0 ) Pub Date : 2021-01-07 , DOI: 10.1088/1478-3975/abc5ad
Rabia Laghmach 1, 2, 3 , Davit A Potoyan 1, 2, 3
Affiliation  

The nucleus of eukaryotic cells harbors active and out of equilibrium environments conducive to diverse gene regulatory processes. On a molecular scale, gene regulatory processes take place within hierarchically compartmentalized sub-nuclear bodies. While the impact of nuclear structure on gene regulation is widely appreciated, it has remained much less clear whether and how gene regulation is impacting nuclear order itself. Recently, the liquid–liquid phase separation emerged as a fundamental mechanism driving the formation of biomolecular condensates, including membrane-less organelles, chromatin territories, and transcriptional domains. The transience and environmental sensitivity of biomolecular condensation are strongly suggestive of kinetic gene-regulatory control of phase separation. To better understand kinetic aspects controlling biomolecular phase-separation, we have constructed a minimalist model of the reactive nucleoplasm. The model is based on the Cahn–Hilliard formulation of ternary protein–RNA–nucleoplasm components coupled to non-equilibrium and spatially dependent gene expression. We find a broad range of kinetic regimes through an extensive set of simulations where the interplay of phase separation and reactive timescales can generate heterogeneous multi-modal gene expression patterns. Furthermore, the significance of this finding is that heterogeneity of gene expression is linked directly with the heterogeneity of length-scales in phase-separated condensates.



中文翻译:

液-液相分离驱动反应性核质的区室化

真核细胞的细胞核具有活跃和失衡的环境,有利于多种基因调控过程。在分子尺度上,基因调控过程发生在分级划分的亚核体内。虽然核结构对基因调控的影响得到广泛认可,但基因调控是否以及如何影响核秩序本身仍不清楚。最近,液-液相分离成为推动生物分子凝聚物形成的基本机制,包括无膜细胞器、染色质区域和转录域。生物分子凝聚的短暂性和环境敏感性强烈暗示了相分离的动力学基因调控控制。为了更好地理解控制生物分子相分离的动力学方面,我们构建了反应性核质的极简模型。该模型基于与非平衡和空间依赖性基因表达耦合的三元蛋白质-RNA-核质成分的 Cahn-Hilliard 公式。我们通过一组广泛的模拟发现了广泛的动力学机制,其中相分离和反应时间尺度的相互作用可以产生异质的多模式基因表达模式。此外,这一发现的意义在于基因表达的异质性与相分离凝聚物中长度尺度的异质性直接相关。该模型基于与非平衡和空间依赖性基因表达耦合的三元蛋白质-RNA-核质成分的 Cahn-Hilliard 公式。我们通过一组广泛的模拟发现了广泛的动力学机制,其中相分离和反应时间尺度的相互作用可以产生异质的多模式基因表达模式。此外,这一发现的意义在于基因表达的异质性与相分离凝聚物中长度尺度的异质性直接相关。该模型基于与非平衡和空间依赖性基因表达耦合的三元蛋白质-RNA-核质成分的 Cahn-Hilliard 公式。我们通过一组广泛的模拟发现了广泛的动力学机制,其中相分离和反应时间尺度的相互作用可以产生异质的多模式基因表达模式。此外,这一发现的意义在于基因表达的异质性与相分离凝聚物中长度尺度的异质性直接相关。我们通过一组广泛的模拟发现了广泛的动力学机制,其中相分离和反应时间尺度的相互作用可以产生异质的多模式基因表达模式。此外,这一发现的意义在于基因表达的异质性与相分离凝聚物中长度尺度的异质性直接相关。我们通过一组广泛的模拟发现了广泛的动力学机制,其中相分离和反应时间尺度的相互作用可以产生异质的多模式基因表达模式。此外,这一发现的意义在于基因表达的异质性与相分离凝聚物中长度尺度的异质性直接相关。

更新日期:2021-01-07
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