RBM4A-SRSF3-MAP4K4 splicing cascade constitutes a molecular mechanism for regulating brown adipogenesis

Hui Yu Peng, Yu Chih Liang, Tse Hua Tan, Huai Chia Chuang, Ying Ju Lin, Jung Chun Lin

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

An increase in mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) reportedly attenuates insulin-mediated signaling which participates in the development of brown adipose tissues (BATs). Nevertheless, the effect of MAP4K4 on brown adipogenesis remains largely uncharacterized. In this study, results of a transcriptome analysis (also referred as RNA-sequencing) showed differential expressions of MAP4K4 or SRSF3 transcripts isolated from distinct stages of embryonic BATs. The discriminative splicing profiles of MAP4K4 or SRSF3 were noted as well in brown adipocytes (BAs) with RNA-binding motif protein 4-knockout (RBM4−/−) compared to the wild-type counterparts. Moreover, the relatively high expressions of authentic SRSF3 transcripts encoding the splicing factor functioned as a novel regulator toward MAP4K4 splicing during brown adipogenesis. The presence of alternatively spliced MAP4K4 variants exerted differential effects on the phosphorylation of c-Jun N-terminal protein kinase (JNK) which was correlated with the differentiation or metabolic signature of BAs. Collectively, the RBM4-SRSF3-MAP4K4 splicing cascade constitutes a novel molecular mechanism in manipulating the development of BAs through related signaling pathways.

Original languageEnglish
Article number2646
JournalInternational Journal of Molecular Sciences
Volume19
Issue number9
DOIs
Publication statusPublished - Sep 6 2018

Fingerprint

Brown Adipocytes
Adipogenesis
splicing
RNA
cascades
Brown Adipose Tissue
adipose tissues
Tissue
Proteins
MAP Kinase Kinase Kinases
Phosphorylation
Insulin
proteins
Protein Kinases
RNA Sequence Analysis
Phosphotransferases
RNA-Binding Proteins
JNK Mitogen-Activated Protein Kinases
Gene Expression Profiling
insulin

Keywords

  • Alternative splicing
  • Brown adipocytes
  • MAP4K4
  • RBM4a
  • SRSF3

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

RBM4A-SRSF3-MAP4K4 splicing cascade constitutes a molecular mechanism for regulating brown adipogenesis. / Peng, Hui Yu; Liang, Yu Chih; Tan, Tse Hua; Chuang, Huai Chia; Lin, Ying Ju; Lin, Jung Chun.

In: International Journal of Molecular Sciences, Vol. 19, No. 9, 2646, 06.09.2018.

Research output: Contribution to journalArticle

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