Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
Volume 1843, Issue 4, Pages 769-779Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamcr.2013.12.018
Keywords
Alternative splicing; BMP7; Brown adipocyte; Insulin receptor; RBM4
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Funding
- Taipei Medical University [TMU100-AE1-B17]
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RNA-binding motif protein 4 (RBM4) reportedly reprograms the tissue-specific splicing network which modulates the development of muscles and pancreatic beta-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-gamma, 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 (Prdm 16 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. (C) 2013 Elsevier B.V. All rights reserved.
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