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Publication : Emerging role for RNA binding motif protein 4 in the development of brown adipocytes.

First Author  Lin JC Year  2014
Journal  Biochim Biophys Acta Volume  1843
Issue  4 Pages  769-79
PubMed ID  24389249 Mgi Jnum  J:210858
Mgi Id  MGI:5571985 Doi  10.1016/j.bbamcr.2013.12.018
Citation  Lin JC, et al. (2014) Emerging role for RNA binding motif protein 4 in the development of brown adipocytes. Biochim Biophys Acta 1843(4):769-79
abstractText  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 (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.
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