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

Jung Chun Lin, Woan Yuh Tarn, Wen Kou Hsieh

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)769-779
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1843
Issue number4
DOIs
Publication statusPublished - Apr 2014

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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