An alternative splicing program promotes adipose tissue thermogenesis

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-induc...

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Main Authors:	Vernia, Santiago, Edwards, Yvonne JK, Han, Myoung Sook, Cavanagh-Kyros, Julie, Barrett, Tamera, Kim, Jason K, Davis, Roger J
Format:	Online
Language:	English
Published:	eLife Sciences Publications, Ltd 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026472/

id	pubmed-5026472
recordtype	oai_dc
spelling	pubmed-50264722016-09-20 An alternative splicing program promotes adipose tissue thermogenesis Vernia, Santiago Edwards, Yvonne JK Han, Myoung Sook Cavanagh-Kyros, Julie Barrett, Tamera Kim, Jason K Davis, Roger J Cell Biology 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. eLife Sciences Publications, Ltd 2016-09-16 /pmc/articles/PMC5026472/ /pubmed/27635635 http://dx.doi.org/10.7554/eLife.17672 Text en © 2016, Vernia et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Vernia, Santiago Edwards, Yvonne JK Han, Myoung Sook Cavanagh-Kyros, Julie Barrett, Tamera Kim, Jason K Davis, Roger J
spellingShingle	Vernia, Santiago Edwards, Yvonne JK Han, Myoung Sook Cavanagh-Kyros, Julie Barrett, Tamera Kim, Jason K Davis, Roger J An alternative splicing program promotes adipose tissue thermogenesis
author_facet	Vernia, Santiago Edwards, Yvonne JK Han, Myoung Sook Cavanagh-Kyros, Julie Barrett, Tamera Kim, Jason K Davis, Roger J
author_sort	Vernia, Santiago
title	An alternative splicing program promotes adipose tissue thermogenesis
title_short	An alternative splicing program promotes adipose tissue thermogenesis
title_full	An alternative splicing program promotes adipose tissue thermogenesis
title_fullStr	An alternative splicing program promotes adipose tissue thermogenesis
title_full_unstemmed	An alternative splicing program promotes adipose tissue thermogenesis
title_sort	alternative splicing program promotes adipose tissue thermogenesis
description	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.
publisher	eLife Sciences Publications, Ltd
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026472/
_version_	1613654039489150976

An alternative splicing program promotes adipose tissue thermogenesis

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