RBM4a-regulated splicing cascade modulates the differentiation and metabolic activities of brown adipocytes

Jung Chun Lin, Yi Han Lu, Yun Ru Liu, Ying Ju Lin

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

RNA-binding motif protein 4a (RBM4a) reportedly reprograms splicing profiles of the insulin receptor (IR) and myocyte enhancer factor 2C (MEF2C) genes, facilitating the differentiation of brown adipocytes. Using an RNA-sequencing analysis, we first compared the gene expressing profiles between wild-type and RBM4a-/- brown adipocytes. The ablation of RBM4a led to increases in the PTBP1, PTBP2 (nPTB), and Nova1 proteins, whereas elevated RBM4a reduced the expression of PTBP1 and PTBP2 proteins in brown adipocytes through an alternative splicing-coupled nonsense-mediated decay mechanism. Subsequently, RBM4a indirectly shortened the half-life of the Nova1 transcript which was comparatively stable in the presence of PTBP2. RBM4a diminished the influence of PTBP2 in adipogenic development by reprogramming the splicing profiles of the FGFR2 and PKM genes. These results constitute a mechanistic understanding of the RBM4a-modulated splicing cascade during the brown adipogenesis.

Original languageEnglish
Article number20665
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Feb 9 2016

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Brown Adipocytes
RNA-Binding Proteins
MEF2 Transcription Factors
Genes
RNA Sequence Analysis
Adipogenesis
Insulin Receptor
Alternative Splicing
RNA-Binding Motifs
Half-Life
Proteins

ASJC Scopus subject areas

  • General

Cite this

RBM4a-regulated splicing cascade modulates the differentiation and metabolic activities of brown adipocytes. / Lin, Jung Chun; Lu, Yi Han; Liu, Yun Ru; Lin, Ying Ju.

In: Scientific Reports, Vol. 6, 20665, 09.02.2016.

Research output: Contribution to journalArticle

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