Choi Sunkyung, Kim Kee K
Department of Biological Sciences, College of Natural Sciences, Keimyung University, Daegu, 42601, Republic of Korea.
Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon, 34134, Republic of Korea.
Genes Genomics. 2025 Sep;47(9):935-951. doi: 10.1007/s13258-025-01661-8. Epub 2025 Aug 4.
Liquid-liquid phase separation (LLPS) segregates the eukaryotic nucleus into membraneless ribonucleoprotein (RNP) condensates that orchestrate multiple stages of gene expression. In contrast to cytoplasmic granules, these nuclear assemblies lie in direct contact with chromatin and nascent pre‑mRNA, granting first‑order control over transcriptional initiation, co‑transcriptional RNA processing, and mRNA export. Consequently, alterations in their biochemical properties can propagate transcriptome‑wide disturbances and increase disease susceptibility. This review synthesizes current knowledge of the molecular composition, architectural scaffolds, and regulatory roles of the four canonical nuclear condensates-nuclear speckles, paraspeckles, Cajal bodies, and histone locus bodies. We discuss how these dynamic hubs accelerate spliceosome assembly, enforce RNA quality control, and reprogram transcription under stress, and we compile evidence that condensate hardening, mislocalization, or compositional rewiring contributes to diverse pathologies. Finally, we evaluate emerging therapeutic strategies that reengineer condensate phase behavior and outline future directions for biophysical and multi-omics approaches needed to translate condensate biology into precision medicine.
液-液相分离（LLPS）将真核细胞核分隔成无膜核糖核蛋白（RNP）凝聚物，这些凝聚物协调基因表达的多个阶段。与细胞质颗粒不同，这些核聚集体与染色质和新生的前体mRNA直接接触，对转录起始、共转录RNA加工和mRNA输出进行一级控制。因此，它们生化特性的改变会在全转录组范围内传播干扰，并增加疾病易感性。本综述综合了目前关于四种典型核凝聚物——核斑点、副斑点、卡哈尔体和组蛋白位点体的分子组成、结构支架和调控作用的知识。我们讨论了这些动态中心如何加速剪接体组装、加强RNA质量控制以及在应激条件下重新编程转录，并且我们整理了证据表明凝聚物硬化、错误定位或组成重排会导致多种病理状况。最后，我们评估了重新设计凝聚物相行为的新兴治疗策略，并概述了将凝聚物生物学转化为精准医学所需的生物物理和多组学方法的未来方向。
