Nature Reviews Molecular Cell Biology ( IF 81.3 ) Pub Date : 2024-05-21 , DOI: 10.1038/s41580-024-00739-7 Jimena Giudice 1, 2 , Hao Jiang 3
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Biomolecular condensates, sometimes also known as membraneless organelles (MLOs), can form through weak multivalent intermolecular interactions of proteins and nucleic acids, a process often associated with liquid–liquid phase separation. Biomolecular condensates are emerging as sites and regulatory platforms of vital cellular functions, including transcription and RNA processing. In the first part of this Review, we comprehensively discuss how alternative splicing regulates the formation and properties of condensates, and conversely the roles of biomolecular condensates in splicing regulation. In the second part, we focus on the spatial connection between splicing regulation and nuclear MLOs such as transcriptional condensates, splicing condensates and nuclear speckles. We then discuss key studies showing how splicing regulation through biomolecular condensates is implicated in human pathologies such as neurodegenerative diseases, different types of cancer, developmental disorders and cardiomyopathies, and conclude with a discussion of outstanding questions pertaining to the roles of condensates and MLOs in splicing regulation and how to experimentally study them.
中文翻译:

通过生物分子凝聚物和无膜细胞器进行剪接调节
生物分子凝聚物,有时也称为无膜细胞器 (MLO),可以通过蛋白质和核酸的弱多价分子间相互作用形成,这一过程通常与液-液相分离有关。生物分子凝聚物正在成为重要细胞功能(包括转录和 RNA 加工)的位点和调节平台。在本综述的第一部分,我们全面讨论了选择性剪接如何调节缩合物的形成和性质,以及生物分子缩合物在剪接调控中的作用。在第二部分中,我们重点介绍剪接调控与核 MLO(如转录凝聚物、剪接凝聚物和核斑点)之间的空间联系。然后,我们讨论了关键研究,这些研究显示了通过生物分子凝聚物的剪接调控如何与人类病理学有关,例如神经退行性疾病、不同类型的癌症、发育障碍和心肌病,并讨论了与凝聚物和 MLO 在剪接调控中的作用以及如何实验研究它们有关的悬而未决的问题。