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一种可变剪接程序促进脂肪组织产热。

An alternative splicing program promotes adipose tissue thermogenesis.

作者信息

Vernia Santiago, Edwards Yvonne Jk, Han Myoung Sook, Cavanagh-Kyros Julie, Barrett Tamera, Kim Jason K, Davis Roger J

机构信息

Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States.

Howard Hughes Medical Institute, Worcester, United States.

出版信息

Elife. 2016 Sep 16;5:e17672. doi: 10.7554/eLife.17672.

DOI:10.7554/eLife.17672
PMID:27635635
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5026472/
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.

摘要

可变前体mRNA剪接增加了转录组的复杂性并控制异构体特异性基因表达。可变剪接是否有助于代谢调节在很大程度上尚不清楚。在这里，我们研究了可变剪接在饮食诱导肥胖发生中的作用。我们发现肥胖诱导的脂肪细胞基因表达变化包括可变前体mRNA剪接。生物信息学分析将部分可变剪接程序与序列特异性NOVA剪接因子联系起来。对脂肪细胞中缺乏NOVA的小鼠的研究证实了这一结论。对缺乏NOVA的小鼠的表型分析表明，脂肪组织产热增加，血糖改善。我们表明，NOVA蛋白介导一个抑制脂肪组织产热的剪接程序。总之，这些数据提供了肥胖中外显子水平分辨率下基因表达的定量分析，并确定了一种有助于调节脂肪组织功能和维持正常血糖的新机制。

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2
A new view of transcriptome complexity and regulation through the lens of local splicing variations.通过局部剪接变异视角对转录组复杂性和调控的新见解。
Elife. 2016 Feb 1;5:e11752. doi: 10.7554/eLife.11752.
3
The pathogenicity of splicing defects: mechanistic insights into pre-mRNA processing inform novel therapeutic approaches.剪接缺陷的致病性：对前体mRNA加工的机制性见解为新型治疗方法提供了依据。
可变剪接：代谢性肝病的标志与治疗契机
Gastroenterol Rep (Oxf). 2025 May 26;13:goaf044. doi: 10.1093/gastro/goaf044. eCollection 2025.
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Alternative Splicing Regulation in Metabolic Disorders.代谢紊乱中的可变剪接调控
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Alternative splicing of uromodulin enhances mitochondrial metabolism for adaptation to stress in kidney epithelial cells.尿调节蛋白的可变剪接增强线粒体代谢以适应肾上皮细胞中的应激。
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