title: Emerging role for RNA binding motif protein 4 in the development of brown adipocytes.
abstract: RNA-binding motif protein 4 (RBM4) reportedly reprograms the tissue-specific splicing network which modulates the development of muscles and pancreatic β-islets. Herein, we report that Rbm4a(-/-) mice exhibited hyperlipidemia accompanied with reduced mass of interscapular brown adipose tissue (iBAT). Elevated RBM4a led to the isoform shift of IR, Ppar-γ, and Pref-1 genes which play pivotal roles in the different stages of adipogenesis. Overexpression of RBM4a enhanced the mitochondrial activity of brown adipocyte-like lineage in the presence of uncoupling agent. RBM4a-ablated adipocytes inversely exhibited impaired development and inefficient energy expenditure. Intriguingly, overexpressed RBM4a induced the expression of brown adipocyte-specific factors (Prdm16 and Bmp7) in white adipocyte-like lineage, which suggested the potential action of RBM4a on the white-to-brown trans-differentiation of adipocytes. In differentiating adipocytes, RBM4a constituted a feed-forward circuit through autoregulating the splicing pattern of its own transcript. Based on these results, we propose the emerging role of RBM4 in regulating the adipocyte-specific splicing events and transcription cascade, which subsequently facilitate the development and function of brown adipocyte-like cells.
authors.affiliation: School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. Electronic address: lin2511@tmu.edu.tw.
authors.forename: Jung-Chun
authors.initials: JC
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Woan-Yuh
authors.initials: WY
authors.lastname: Tarn
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Wen-Kou
authors.initials: WK
authors.lastname: Hsieh
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology / Q000378:metabolism*; D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005802:Genes, MHC Class II; D006949:Hyperlipidemias / Q000235:genetics / Q000473:pathology; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D032342:Muscle Cells / Q000378:metabolism*; D047495:PPAR gamma / Q000096:biosynthesis; D061251:Primary Cell Culture; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D047495:PPAR gamma; C473692:RBM4 protein, human; D016601:RNA-Binding Proteins
keywords: Alternative splicing; BMP7; Brown adipocyte; Insulin receptor; RBM4