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Biochim Biophys Acta. 2014 Apr;1843(4):769-79. doi: 10.1016/j.bbamcr.2013.12.018. Epub 2014 Jan 2.

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

Author information

  • 1School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. Electronic address: lin2511@tmu.edu.tw.
  • 2Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

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.

KEYWORDS:

Alternative splicing; BMP7; Brown adipocyte; Insulin receptor; RBM4

PMID:
24389249
DOI:
10.1016/j.bbamcr.2013.12.018
[PubMed - indexed for MEDLINE]
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