Dewpoint Therapeutics, Boston, MA, USA.
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cell Chem Biol. 2024 Sep 19;31(9):1593-1609. doi: 10.1016/j.chembiol.2024.08.009.
Biomolecular condensates are dynamic membraneless organelles that compartmentalize proteins and RNA molecules to regulate key cellular processes. Diverse RNA species exert their effects on the cell by their roles in condensate formation and function. RNA abnormalities such as overexpression, modification, and mislocalization can lead to pathological condensate behaviors that drive various diseases, including cancer, neurological disorders, and infections. Here, we review RNA's role in condensate biology, describe the mechanisms of RNA-induced condensate dysregulation, note the implications for disease pathogenesis, and discuss novel therapeutic strategies. Emerging approaches to targeting RNA within condensates, including small molecules and RNA-based therapies that leverage the unique properties of condensates, may revolutionize treatment for complex diseases.
生物分子凝聚物是动态的无膜细胞器，可分隔蛋白质和 RNA 分子，以调节关键的细胞过程。不同的 RNA 种类通过在凝聚物形成和功能中的作用发挥其对细胞的影响。RNA 异常，如过表达、修饰和定位错误，可导致病理性凝聚物行为，从而引发各种疾病，包括癌症、神经紊乱和感染。在这里，我们综述了 RNA 在凝聚物生物学中的作用，描述了 RNA 诱导的凝聚物失调的机制，指出了其对疾病发病机制的影响，并讨论了新的治疗策略。新兴的靶向凝聚物内 RNA 的方法，包括利用凝聚物独特性质的小分子和基于 RNA 的疗法，可能会彻底改变复杂疾病的治疗方法。
