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<p>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.</p>

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Nuclear ribonucleoprotein condensates as platforms for gene expression regulation

  • 期刊论文

  • 发表日期：

    2025年8月4日

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  • Sunkyung Choi,
  • Kee K. Kim

摘要

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.