RBM4 Promotes Pancreas Cell Differentiation and Insulin Expression

  title={RBM4 Promotes Pancreas Cell Differentiation and Insulin Expression},
  author={Jung-Chun Lin and Yu-Ting Yan and Wen-Kou Hsieh and Pey-Jey Peng and Chun-Hao Su and Woan-Yuh Tarn},
  journal={Molecular and Cellular Biology},
  pages={319 - 327}
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… 
RBM4a-regulated splicing cascade modulates the differentiation and metabolic activities of brown adipocytes
RBM4a diminished the influence of PTBP2 in adipogenic development by reprogramming the splicing profiles of the FGFR2 and PKM genes, and indirectly shortened the half-life of the Nova1 transcript which was comparatively stable in the presence ofPTBP2.
RBM4 Regulates Neuronal Differentiation of Mesenchymal Stem Cells by Modulating Alternative Splicing of Pyruvate Kinase M
It is found that the splice isoform change of the metabolic enzyme pyruvate kinase M (PKM) from PKM2 to PKM1 occurs during brain development and is impaired in R BM4-deficient brains, and RBM4 plays an important role in the PKM isoform switch and the change in mitochondrial energy production during neuronal differentiation.
RBM4 modulates the proliferation and expression of inflammatory factors via the alternative splicing of regulatory factors in HeLa cells
RBM4 can mediate the inflammatory response via splicing regulation, which adds to the understanding of the critical role of RBM4 in cancer complicated by inflammation.
RBM4-MEF2C network constitutes a feed-forward circuit that facilitates the differentiation of brown adipocytes
The results indicated that the RBM4-MEF2C-miR-1 network constitutes a novel mechanism which programs the gene expression profile toward the development of brown adipocytes.
RBM4 Modulates Radial Migration via Alternative Splicing of Dab1 during Cortex Development
It is shown that the full-length Dab1, but not exon 7/8-truncated Dab 1, rescued neuronal migration defects in RBM4-depleted neurons, indicating that R BM4 plays a role in neuronal migration via modulating the expression of Dab2 splice isoforms.
Insulin receptor isoform switching in intestinal stem cells, progenitors, differentiated lineages and tumors: evidence that IR-B limits proliferation
Evidence is provided that IR-B expression is significantly lower in highly proliferative IESCs and progenitor cells versus post-mitotic, differentiated IECs and in subconfluent and undifferentiated versus differentiated Caco-2 cells, and new evidence is provided for the roles ofIR-B to limit proliferation of CRC cells.


Combined expression of transcription factors induces AR42J-B13 cells to differentiate into insulin-producing cells.
It is demonstrated that Ngn3 expressed together with Nkx6.1 or MafA induces AR42J-B13 cells to differentiate into insulin-producing cells, supporting the use of these cells as a model system for studying beta-cell differentiation in vitro.
Regulation of insulin gene transcription
It is clear that much more study is required to fully comprehend the mechanisms involved in the regulated-expression of the insulin gene in the beta cell to prevent its impairment in diabetes.
Multiple roles of RBM4 in muscle cell differentiation.
Overexpression of RBM4 promotes muscle cell differentiation, suggesting that RBM2 acts as a positive myogenic regulator, and recent data regarding how R BM4 operates are discussed.
Expression of dominant negative form of PAX4 in human insulinoma.
It is shown that PAX4 mRNA was highly expressed in human insulinoma tissues, whereas little if any mRNA was expressed in normal islets, which implies a role of PAX4 and PAX4v expression in tumorigenesis and development of insulinoma.
Chronic hyperglycemia impairs insulin secretion by affecting insulin receptor expression, splicing, and signaling in RIN β‐cell line and human islets of Langerhans
  • M. Hribal, L. Perego, G. Sesti
  • Biology, Medicine
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2003
The results demonstrate that the insulin receptor is localized in insulin secretory vescicles in human pancreatic β‐cells and suggest that changes in early steps of insulin receptor signaling may play a role in determining β‐cell dysfunction caused by chronic hyperglycemia.
Insulin Gene Expression Is Regulated by DNA Methylation
The findings suggest that insulin promoter CpG demethylation may play a crucial role in beta cell maturation and tissue-specific insulin gene expression.
Exon Selection in α-Tropomyosin mRNA Is Regulated by the Antagonistic Action of RBM4 and PTB
It is demonstrated that RBM4 can activate the selection of skeletal muscle-specific exons, possibly via binding to intronic pyrimidine-rich elements and antagonized this PTB-mediated exon exclusion likely by competing with PTB for binding to a CU-rich element.
Exon selection in alpha-tropomyosin mRNA is regulated by the antagonistic action of RBM4 and PTB.
It is demonstrated that RBM4 can activate the selection of skeletal muscle-specific exons, possibly via binding to intronic pyrimidine-rich elements, and antagonized this PTB-mediated exon exclusion likely by competing with PTB for binding to a CU-rich element.
Glucose Regulation of Insulin Gene Transcription and Pre-mRNA Processing in Human Islets
The data suggest that pre-mRNA species may be a more reliable reflection of acute changes to human insulin gene transcriptional rates and that glucose acutely enhances insulin transcription by a mechanism that enhances chromatin accessibility and leads to recruitment of basal transcriptional machinery.