Program in Molecular Medicine; UMass Metabolic Network
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Genetics and Genomics
Alternative pre-mRNA splicing expands the complexity of the transcriptome and controls isoform-specific gene expression. Whether alternative splicing contributes to metabolic regulation is largely unknown. Here we investigated the contribution of alternative splicing to the development of diet-induced obesity. We found that obesity-induced changes in adipocyte gene expression include alternative pre-mRNA splicing. Bioinformatics analysis associated part of this alternative splicing program with sequence specific NOVA splicing factors. This conclusion was confirmed by studies of mice with NOVA deficiency in adipocytes. Phenotypic analysis of the NOVA-deficient mice demonstrated increased adipose tissue thermogenesis and improved glycemia. We show that NOVA proteins mediate a splicing program that suppresses adipose tissue thermogenesis. Together, these data provide quantitative analysis of gene expression at exon-level resolution in obesity and identify a novel mechanism that contributes to the regulation of adipose tissue function and the maintenance of normal glycemia.
JNK, NOVA, adipocyte, cell biology, high fat diet, human, mouse, pre-mRNA splicing, thermogenesis
DOI of Published Version
Elife. 2016 Sep 16;5. pii: e17672. doi: 10.7554/eLife.17672. Link to article on publisher's site
Vernia, Santiago; Edwards, Yvonne J. K.; Han, Myoung Souk; Cavanagh-Kyros, Julie; Barrett, Tamera; Kim, Jason K.; and Davis, Roger J., "An alternative splicing program promotes adipose tissue thermogenesis" (2016). University of Massachusetts Medical School Faculty Publications. 1050.
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