SPlicing Regulation Through Biomolecular Condensates and Membraneless Organelles

SPlicing Regulation Through Biomolecular Condensates and Membraneless Organelles

2024 September | Jimena Giudice, Hao Jiang
Biomolecular condensates and membraneless organelles (MLOs) play a critical role in splicing regulation. These structures, formed through weak multivalent interactions, are involved in various cellular functions, including transcription and RNA processing. The review discusses how alternative splicing regulates condensate formation and properties, and how condensates influence splicing. It also explores the spatial connections between splicing regulation and nuclear bodies like transcriptional condensates, splicing condensates, and nuclear speckles. Key research highlights the involvement of condensates in human pathologies such as neurodegenerative diseases, cancers, developmental disorders, and cardiomyopathies. The review concludes with open questions regarding the roles of condensates and MLOs in splicing regulation and how to study them experimentally. RBPs, particularly those with low complexity domains, are central to phase separation and splicing regulation. Alternative splicing of RBPs can influence their phase separation capacity and splicing functions. The review also discusses how condensates regulate splicing through dynamic storage, concentration, and sequestration of splicing factors. The spatial organization of splicing is influenced by nuclear speckles and other MLOs, which are involved in splicing regulation and gene expression. The review highlights the importance of condensate properties in splicing regulation and the potential for dysregulation to contribute to disease. The study of condensates and their role in splicing is an emerging field with significant implications for understanding and treating diseases.Biomolecular condensates and membraneless organelles (MLOs) play a critical role in splicing regulation. These structures, formed through weak multivalent interactions, are involved in various cellular functions, including transcription and RNA processing. The review discusses how alternative splicing regulates condensate formation and properties, and how condensates influence splicing. It also explores the spatial connections between splicing regulation and nuclear bodies like transcriptional condensates, splicing condensates, and nuclear speckles. Key research highlights the involvement of condensates in human pathologies such as neurodegenerative diseases, cancers, developmental disorders, and cardiomyopathies. The review concludes with open questions regarding the roles of condensates and MLOs in splicing regulation and how to study them experimentally. RBPs, particularly those with low complexity domains, are central to phase separation and splicing regulation. Alternative splicing of RBPs can influence their phase separation capacity and splicing functions. The review also discusses how condensates regulate splicing through dynamic storage, concentration, and sequestration of splicing factors. The spatial organization of splicing is influenced by nuclear speckles and other MLOs, which are involved in splicing regulation and gene expression. The review highlights the importance of condensate properties in splicing regulation and the potential for dysregulation to contribute to disease. The study of condensates and their role in splicing is an emerging field with significant implications for understanding and treating diseases.
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Understanding Splicing regulation through biomolecular condensates and membraneless organelles.