Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR 999077, China.
ACS Macro Lett. 2022 Apr 19;11(4):562-567. doi: 10.1021/acsmacrolett.2c00167. Epub 2022 Apr 6.
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.
液-液相分离（LLPS）成为生物组织的基本基础机制，特别是无膜细胞器（MLO）的形成，其中包含作为支架的固有无序蛋白质（IDP）。核酸是 MLO 的组成生物大分子，对正常细胞功能以及由异常相行为引起的病理生理学有广泛的影响。利用源自 IDP 模拟聚合物-寡肽杂合（IPH）的 LLPS 的最小人工无膜细胞器（AMLO），我们研究了具有不同长度和序列变化的核酸对 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，即形成、形态、流动性和动力学的调节倾向。DNA 和 RNA 都可以增强 AMLO 的 LLPS，而与 RNA 相比，DNA 更倾向于固化并降低其动力学。这些发现表明它有可能成为理解核酸与天然 MLO 之间相互作用以及研究涉及 MLO 的疾病的分子机制的简洁模型系统。
