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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/219694
The splicing factor SF3B1 is involved in brown adipocyte thermogenic activation
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The ability of alternative splicing mechanisms to control gene expression is increasingly being recognized as relevant for adipose tissue function. The expression of SF3B1, a key component of the SF3B complex directly involved in spliceosome formation, was previously reported to be significantly induced in brown adipose tissue under cold-induced thermogenic activation. Here, we identify that noradrenergic cAMP-mediated thermogenic stimulation increases SF3B1 expression in brown and beige adipocytes. We further show that pladienolide-B, a drug that binds SF3B1 to inhibit pre-mRNA splicing by targeting the SF3B complex, down-regulates key components of the thermogenic machinery (e.g., UCP1 gene expression), differentially alters the expression of alternative splicing-regulated transcripts encoding molecular actors involved in the oxidative metabolism of brown adipocytes (e.g., peroxisome proliferator-activated receptor-gamma co-activator-alpha [PGC-1α] and cytochrome oxidase subunit 7a genes), and impairs the respiratory activity of brown adipocytes. Similar alterations were found in brown adipocytes with siRNA-mediated knockdown of SF3B1 protein levels. Our findings collectively indicate that SF3B1 is a key factor in the appropriate thermogenic activation of differentiated brown adipocytes. This work exemplifies the importance of splicing processes in adaptive thermogenesis and suggests that pharmacological tools, such as pladienolide-B, may be used to modulate brown adipocyte thermogenic activity.
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CASTELLÁ GINER, Moisés, MESTRES ARENAS, Alberto, GAVALDÀ I NAVARRO, Aleix, BLASCO ROSET, Albert, QUESADA LÓPEZ, Tania paloma, ROMERO-CARRAMIÑANA, Inés, GIRALT I OMS, Marta, VILLARROYA I GOMBAU, Francesc, CEREIJO TÉLLEZ, Rubén. The splicing factor SF3B1 is involved in brown adipocyte thermogenic activation. _Biochemical Pharmacology_. 2024. Vol. 220, núm. 1-11. [consulta: 24 de novembre de 2025]. ISSN: 0006-2952. [Disponible a: https://hdl.handle.net/2445/219694]