Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10802073 | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | 2014 | 11 Pages |
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 Rbm4aâ/â 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.
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Authors
Jung-Chun Lin, Woan-Yuh Tarn, Wen-Kou Hsieh,