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
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-液相分离相关。生物分子凝聚体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中,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,以及反过来生物分子缩合物在剪接调节中的作用。在第二部分中,我们重点研究剪接调控与核MLO(例如转录凝聚物、剪接凝聚物和核斑点)之间的空间联系。然后,我们讨论了一些关键研究,这些研究表明生物分子缩合物的剪接调节如何与神经退行性疾病、不同类型的癌症、发育障碍和心肌病等人类病理学有关,最后讨论了与缩合物和 MLO 在剪接中的作用有关的突出问题调节以及如何通过实验研究它们。