近日，美国纽约州立大学Priya R. Banerjee团队揭示了在多组分生物分子凝聚物的核心内部，同型RNA聚类伴随着液体到固体的转变。2025年7月2日出版的《自然-化学》杂志发表了这项成果。

RNA驱动的凝聚在细胞内核糖核蛋白颗粒的组织和调节中起着核心作用。这一过程的中断——比如重复扩增RNA的异常聚集——与许多神经系统疾病有关。

研究组分析了生物分子凝聚物在不可逆RNA聚集中的作用。结果发现生理相关和疾病相关的重复RNA在多组分凝聚物中自发地经历年龄依赖的渗透转变，形成纳米尺度的细胞。同型RNA细胞驱动多相凝析结构的出现，一个富含RNA的固体核被一个缺乏RNA的流体壳包围。RNA测序的时间尺度由序列、二级结构和重复长度决定。

重要的是，G3BP1作为应激颗粒的核心支架，为同型RNA - RNA相互作用引入了异型缓冲，并以不依赖于ATP的方式阻止RNA聚集。该研究表明，生物分子凝聚物可以作为RNA聚集的位点，并强调了RNA结合蛋白对异常RNA相变的伴侣样功能。

附：英文原文

Title: Homotypic RNA clustering accompanies a liquid-to-solid transition inside the core of multi-component biomolecular condensates

Author: Mahendran, Tharun Selvam, Wadsworth, Gable M., Singh, Anurag, Gupta, Ritika, Banerjee, Priya R.

Issue&Volume: 2025-07-02

Abstract: RNA-driven condensation plays a central role in organizing and regulating ribonucleoprotein granules within cells. Disruptions to this process—such as the aberrant aggregation of repeat-expanded RNA—are associated with numerous neurological disorders. Here we study the role of biomolecular condensates in irreversible RNA aggregation. We find that physiologically relevant and disease-associated repeat RNAs spontaneously undergo an age-dependent percolation transition inside multi-component condensates to form nanoscale clusters. Homotypic RNA clusters drive the emergence of multi-phasic condensate structures, with an RNA-rich solid core surrounded by an RNA-depleted fluid shell. The timescale of RNA clustering is determined by sequence, secondary structure and repeat length. Importantly, G3BP1, the core scaffold of stress granules, introduces heterotypic buffering to homotypic RNA–RNA interactions and prevents RNA clustering in an ATP-independent manner. Our work suggests that biomolecular condensates can act as sites for RNA aggregation and highlights the chaperone-like function of RNA-binding proteins against aberrant RNA phase transitions.

DOI: 10.1038/s41557-025-01847-3

Source: https://www.nature.com/articles/s41557-025-01847-3