Nucleic Acids Modulate Liquidity and Dynamics of Artificial Membraneless Organelles,ACS Macro Letters

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Nucleic Acids Modulate Liquidity and Dynamics of Artificial Membraneless Organelles
ACS Macro Letters ( IF 5.1 ) Pub Date : 2022-04-06 , DOI: 10.1021/acsmacrolett.2c00167
Jianhui Liu ₁ , Fariza Zhorabek ₁ , Ying Chau ₁

Affiliation

Liquid–liquid phase separation (LLPS) emerges as a fundamental underlying mechanism for the biological organization, especially the formation of membraneless organelles (MLOs) hosting intrinsically disordered proteins (IDPs) as scaffolds. Nucleic acids are compositional biomacromolecules of MLOs with wide implications in normal cell functions as well as in pathophysiology caused by aberrant phase behavior. Exploiting a minimalist artificial membraneless organelles (AMLO) from LLPS of IDP-mimicking polymer–oligopeptide hybrid (IPH), we investigated the effect of nucleic acids with different lengths and sequence variations on AMLO. The behavior of this AMLO in the presence of DNAs and RNAs resembled natural MLOs in multiple aspects, namely, modulated propensity of formation, morphology, liquidity, and dynamics. Both DNA and RNA could enhance the LLPS of AMLO, while compared with RNA, DNA had a higher tendency to solidify and diminish dynamics thereof. These findings suggest its potential as a concise model system for the understanding of the interaction between nucleic acids and natural MLOs and for studying the molecular mechanism of diseases involving MLOs.

中文翻译：

核酸调节人工无膜细胞器的流动性和动力学

液-液相分离 (LLPS) 成为生物组织的基本潜在机制，尤其是形成以固有无序蛋白质 (IDP) 作为支架的无膜细胞器 (MLO)。核酸是 MLO 的组成生物大分子，在正常细胞功能以及由异常相行为引起的病理生理学中具有广泛的意义。利用 IDP 模拟聚合物-寡肽杂合体 (IPH) 的 LLPS 中的极简人工无膜细胞器 (AMLO)，我们研究了不同长度和序列变异的核酸对 AMLO 的影响。这种 AMLO 在 DNA 和 RNA 存在下的行为在多个方面类似于天然 MLO，即受调节的形成倾向、形态、流动性和动力学。DNA和RNA都可以增强AMLO的LLPS，而与RNA相比，DNA具有更高的凝固和减弱其动力学的趋势。这些发现表明，它有可能作为一个简洁的模型系统，用于理解核酸与天然 MLO 之间的相互作用以及研究涉及 MLO 的疾病的分子机制。

更新日期：2022-04-06

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