Liao Yue, Fan Chunyu, Zheng Jiaxin, Liu Caixia, Zhu Weiping, Xu Yufang, Qian Xuhong, Yang Yangyang
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
J Mater Chem B. 2025 Jan 29;13(5):1744-1752. doi: 10.1039/d4tb02161d.
Biomolecular condensates (BCs) are crucial membraneless organelles formed through the process of liquid-liquid phase separation (LLPS) involving proteins and nucleic acids. These LLPS processes are tightly linked with essential cellular activities. Stress granules (SGs), functioning as cytoplasmic BCs, play indispensable roles in maintaining cellular homeostasis and are implicated in diseases like cancers and neurodegenerative disorders. However, devices that can regulate SG LLPS are lacking. Herein, a triangular prism-shaped DNA nanostructure containing polythymidine (ΔDNA) is presented as a nanodevice to investigate the LLPS process of reconstructed SGs (rSGs), a mixture of marker protein G3BP1 and total RNAs. Our observations reveal that the concentration threshold required for rSG LLPS decreases upon addition of ΔDNA, suggesting an enhancement in SG LLPS efficiency. It is speculated that ΔDNA can concentrate mRNAs onto its surface polyT hybridization with poly-adenosine sequences (polyA) in mRNAs. This alteration in the spatial distribution of mRNAs subsequently affects the multivalency interactions between G3BP1 and mRNAs. Furthermore, ΔDNA exhibits excellent colocalization with cytoplasmic SGs under stressed conditions. This DNA-based nanodevice presents a new artificial approach for the targeted regulation of BC LLPS and holds promise for future studies focusing on BCs.
生物分子凝聚物（BCs）是通过涉及蛋白质和核酸的液-液相分离（LLPS）过程形成的关键无膜细胞器。这些LLPS过程与基本的细胞活动紧密相连。应激颗粒（SGs）作为细胞质BCs，在维持细胞内稳态中发挥不可或缺的作用，并与癌症和神经退行性疾病等疾病有关。然而，目前缺乏能够调节SG LLPS的装置。在此，一种含有聚胸腺嘧啶的三棱柱形DNA纳米结构（ΔDNA）被作为一种纳米装置提出，用于研究重组应激颗粒（rSGs，标记蛋白G3BP1和总RNA的混合物）的LLPS过程。我们的观察结果表明，添加ΔDNA后，rSG LLPS所需的浓度阈值降低，这表明SG LLPS效率有所提高。据推测，ΔDNA可以通过与mRNA中的聚腺苷酸序列（polyA）进行聚T杂交，将mRNA浓缩在其表面。mRNA空间分布的这种改变随后会影响G3BP1与mRNA之间的多价相互作用。此外，在应激条件下，ΔDNA与细胞质SGs表现出良好的共定位。这种基于DNA的纳米装置为靶向调节BC LLPS提供了一种新的人工方法，并有望用于未来针对BCs的研究。
