RNA-associated nuclear condensates: Where the nucleus keeps its RNAs in check

Noncoding RNAs (ncRNAs) are emerging regulators of cellular processes and stress response by controlling chromatin architecture and gene expression. Recent studies have revealed that these ncRNAs functions are closely associated with nuclear condensates, membrane-less compartments formed by liquid-liquid phase separation (LLPS) that provide a specialized subnuclear environment for genome organization as well as transcriptional and post-transcriptional regulation. Disruption of RNA-mediated nuclear condensates is increasingly linked to human diseases, including neurodegenerative disease and cancer, emphasizing their essential role in maintaining cellular homeostasis. Advances in high-resolution microscopy and high-throughput sequencing have elucidated subcompartmental structures and genetic components of nuclear condensates by identifying associated RNA molecules and providing the details of RNA-protein interactions at a single-nucleotide resolution. We now understand that ncRNAs act as scaffolds that recruit RNA-binding proteins with intrinsically disordered domains to trigger the nucleation event for LLPS, resulting in the formation of nuclear condensates. In this review, we summarize how RNAs and RNA-binding proteins contribute to RNA-mediated nuclear condensate formation via LLPS and support their regulatory functions.