RBM4 promotes pancreas cell differentiation and insulin expression

Jung Chun Lin, Yu Ting Yan, Wen Kou Hsieh, Pey Jey Peng, Chun Hao Su, Woan Yuh Tarna

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The RNA-binding protein RNA-binding motif protein 4 (RBM4) modulates alternative splicing of muscle-specific mRNA isoforms during muscle cell differentiation. To better understand the physiological function of RBM4, we exploited a gene knockout strategy in the present study. Mice with targeted disruption of one of the two Rbm4 genes exhibited hyperglycemia coincident with reduced levels of serum insulin and reduced size of pancreatic islets. The embryonic pancreases of Rbm4-deficient mice showed reduced expression or aberrant splicing of many transcripts encoding factors required for pancreas cell differentiation and function. Using pancreatic acinar AR42J cells, we demonstrated that RBM4 promoted insulin gene expression by altering the isoform balance of the transcription factors Isl1 and Pax4 via alternative splicing control. RBM4 overexpression was sufficient to convert AR42J cells into insulin-producing cells. Moreover, RBM4 may mediate glucose-induced insulin expression and insulin receptor isoform switches. These results suggest that RBM4 may have role in promoting pancreas cell differentiation and endocrine function, essentially via alternative splicing regulation.

Original languageEnglish
Pages (from-to)319-327
Number of pages9
JournalMolecular and Cellular Biology
Volume33
Issue number2
DOIs
Publication statusPublished - Jan 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Lin, J. C., Yan, Y. T., Hsieh, W. K., Peng, P. J., Su, C. H., & Tarna, W. Y. (2013). RBM4 promotes pancreas cell differentiation and insulin expression. Molecular and Cellular Biology, 33(2), 319-327. https://doi.org/10.1128/MCB.01266-12