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An alternative splicing program promotes adipose tissue thermogenesis

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Title: An alternative splicing program promotes adipose tissue thermogenesis
Authors: Vernia, S
Edwards, YJK
Han, MS
Cavanagh-Kyros, J
Barrett, T
Kim, JK
Davis, RJ
Item Type: Journal Article
Abstract: 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.
Issue Date: 16-Sep-2016
Date of Acceptance: 14-Aug-2016
URI: http://hdl.handle.net/10044/1/61116
DOI: https://dx.doi.org/10.7554/eLife.17672
ISSN: 2050-084X
Publisher: ELIFE SCIENCES PUBLICATIONS LTD
Journal / Book Title: ELIFE
Volume: 5
Copyright Statement: © 2016, Vernia et al. This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.
Keywords: Science & Technology
Life Sciences & Biomedicine
Biology
Life Sciences & Biomedicine - Other Topics
SIGNAL-TRANSDUCTION PATHWAY
RNA-SEQ DATA
METABOLIC-REGULATION
PROTEIN-INTERACTION
REGULATORY NETWORK
INSULIN-RESISTANCE
HITS-CLIP
JNK
GENE
EXPRESSION
Publication Status: Published
Open Access location: https://elifesciences.org/articles/17672
Article Number: ARTN e17672
Online Publication Date: 2016-09-16
Appears in Collections:Clinical Sciences
Molecular Sciences



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