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Publication : An alternative splicing program promotes adipose tissue thermogenesis.

First Author  Vernia S Year  2016
Journal  Elife Volume  5
PubMed ID  27635635 Mgi Jnum  J:236975
Mgi Id  MGI:5810478 Doi  10.7554/eLife.17672
Citation  Vernia S, et al. (2016) An alternative splicing program promotes adipose tissue thermogenesis. Elife 5:e17672
abstractText  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.
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