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

JC Lin, WY Tarn, WK Hsieh - … et Biophysica Acta (BBA)-Molecular Cell …, 2014 - Elsevier
JC Lin, WY Tarn, WK Hsieh
Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 2014Elsevier
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 …
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.
Elsevier