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National Institute of Environmental Health Sciences

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Publication Detail

Title: Regulation of corepressor alternative mRNA splicing by hormonal and metabolic signaling.

Authors: Snyder, Chelsea A; Goodson, Michael L; Schroeder, Amy C; Privalsky, Martin L

Published In Mol Cell Endocrinol, (2015 Sep 15)

Abstract: Alternative mRNA splicing diversifies the products encoded by the NCoR and SMRT corepressor loci. There is a programmed alteration in NCoR mRNA splicing during adipocyte differentiation from an NCoRω isoform, which contains three nuclear receptor interaction domains, to an NCoRδ isoform that contains two nuclear receptor interaction domains. This alternative mRNA splicing of NCoR has profound effects on adiposity and on diabetes in mouse models. We report here that dexamethasone, a powerful regulator of metabolism and of adipocyte differentiation, confers this change in NCoR mRNA splicing in cultured adipocytes. We also demonstrate that changes in dietary components can consistently, if moderately, modulate the total transcript levels and the mRNA splicing of NCoR and SMRT in both cultured cells and intact mice. This ability of alternative corepressor mRNA splicing to respond to nutritional changes confirms its importance in regulating glucose and lipid metabolism, and its promise as a therapeutic candidate for metabolic disorders such as type 2 diabetes.

PubMed ID: 26166430 Exiting the NIEHS site

MeSH Terms: 3T3-L1 Cells; Adipocytes/cytology; Adipocytes/metabolism*; Alternative Splicing/drug effects*; Alternative Splicing/genetics; Animals; Cell Differentiation/drug effects; Cell Differentiation/genetics; Dexamethasone/pharmacology*; Diabetes Mellitus, Type 2/drug therapy; Diabetes Mellitus, Type 2/genetics; Diabetes Mellitus, Type 2/pathology; Glucose/metabolism; Glucose/pharmacology*; Lipid Metabolism/drug effects; Lipid Metabolism/genetics; Mice; Nuclear Receptor Co-Repressor 1/genetics; Nuclear Receptor Co-Repressor 1/metabolism*; Nuclear Receptor Co-Repressor 2/genetics; Nuclear Receptor Co-Repressor 2/metabolism*; RNA, Messenger/genetics; RNA, Messenger/metabolism*; Signal Transduction/drug effects*; Signal Transduction/genetics

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