近日，瑞士苏黎世联邦理工学院Frédéric H-.T. Allain团队报道了水检测核磁共振实现对重复扩增的RNA缩合物进行动态观察。2025年10月15日出版的《自然-化学》杂志发表了这项成果。

RNA缩合与受三核苷酸或六核苷酸重复序列基因组扩增影响的细胞中神经毒性RNA灶的形成有关。然而，重复膨胀RNA凝聚物的生物物理性质尚不清楚。

使用CAG重复扩增RNA作为模型系统，研究组发现这些RNA凝聚物不能用传统的核磁共振技术观察到。因此，他们开发了一种基于水检测半固体磁化转移的核磁共振方法，用于体外检测和表征RNA凝聚体。该方法被称为半固体磁化转移冷凝物检测（CONDENSE-MT），适用范围广，灵敏度高，不需要直接观察感兴趣的生物分子。利用condenst - mt，研究组可以得到有关RNA凝聚物的动态信息，如浓缩RNA的相对数量和翻滚速率、质子-溶剂交换动力学以及在凝聚物中短暂结合的水分子的数量。研究组发现相分离极大地减少了分子翻滚，并且是由RNA和Mg²⁺之间的异型相互作用驱动的。研究组进一步表明，增加CAG重复次数会降低冷凝水的水化作用。

附：英文原文

Title: Water-detected NMR allows dynamic observations of repeat-expansion RNA condensates

Author: Schmoll, Johannes, Novakovic, Mihajlo, Allain, Frdric H-.T.

Issue&Volume: 2025-10-15

Abstract: RNA condensation is implicated in the formation of neurotoxic RNA foci in cells affected by genomic expansions of trinucleotide or hexanucleotide repeats. However, the biophysical properties of repeat-expansion RNA condensates are poorly understood. Using CAG repeat-expansion RNA as a model system, we show that these RNA condensates cannot be observed with conventional nuclear magnetic resonance techniques. Therefore, we developed a nuclear magnetic resonance approach, based on water-detected semi-solid magnetization transfer, to detect and characterize RNA condensates in vitro. Our method, termed condensate detection by semi-solid magnetization transfer (CONDENSE-MT), is broadly applicable, highly sensitive and does not require direct observation of the biomolecules of interest. Using CONDENSE-MT, we could obtain dynamic information about RNA condensates, such as the relative amount and the tumbling rate of condensed RNA, the proton–solvent exchange kinetics and the amount of water molecules transiently bound in the condensate. We find that phase separation dramatically decreases molecular tumbling and is driven by heterotypic interactions between RNA and Mg2+. We further show that increasing CAG repeats decreases condensate hydration.

DOI: 10.1038/s41557-025-01968-9

Source: https://www.nature.com/articles/s41557-025-01968-9