胆固醇稳态调控中的可变剪接。
Alternative splicing in the regulation of cholesterol homeostasis.
机构信息
Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
出版信息
Curr Opin Lipidol. 2013 Apr;24(2):147-52. doi: 10.1097/MOL.0b013e32835cf284.
Abstract
PURPOSE OF REVIEW
With the advent of whole-transcriptome sequencing, or RNA-seq, we now know that alternative splicing is a generalized phenomenon, with nearly all multiexonic genes subject to alternative splicing. In this review, we highlight recent studies examining alternative splicing as a modulator of cellular cholesterol homeostasis and as an underlying mechanism of dyslipidemia.
RECENT FINDINGS
A number of key genes involved in cholesterol metabolism are known to undergo functionally relevant alternative splicing. Recently, we have identified coordinated changes in alternative splicing in multiple genes in response to alterations in cellular sterol content. We and others have implicated several splicing factors as regulators of lipid metabolism. Furthermore, a number of cis-acting human gene variants that modulate alternative splicing have been implicated in a variety of human metabolic diseases.
SUMMARY
Alternative splicing is of importance in various types of genetically influenced dyslipidemias and in the regulation of cellular cholesterol metabolism.
摘要
目的综述
随着全转录组测序或 RNA-seq 的出现，我们现在知道可变剪接是一种普遍现象，几乎所有多外显子基因都受到可变剪接的影响。在这篇综述中，我们强调了最近的研究，这些研究检查了可变剪接作为细胞胆固醇稳态的调节剂和血脂异常的潜在机制。
最近的发现
许多参与胆固醇代谢的关键基因已知会发生具有功能相关性的可变剪接。最近，我们已经确定了细胞固醇含量变化时多个基因的可变剪接的协调变化。我们和其他人已经将几种剪接因子确定为脂质代谢的调节剂。此外，一些调节可变剪接的顺式作用人类基因变异体与多种人类代谢疾病有关。
总结
可变剪接在各种遗传性血脂异常和细胞胆固醇代谢的调节中很重要。
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本文引用的文献
1
Response to Brosch et al.对布罗施等人的回应
Cell Metab. 2012 Mar 7;15(3):267-269. doi: 10.1016/j.cmet.2012.02.005.
2
Function of alternative splicing.可变剪接的功能。
Gene. 2013 Feb 1;514(1):1-30. doi: 10.1016/j.gene.2012.07.083. Epub 2012 Aug 15.
3
SFRS10--a splicing factor gene reduced in human obesity?SFRS10——一种在人类肥胖中表达降低的剪接因子基因？
Cell Metab. 2012 Mar 7;15(3):265-6; author reply 267-9. doi: 10.1016/j.cmet.2012.02.002.
4
Molecular and functional analysis of two new MTTP gene mutations in an atypical case of abetalipoproteinemia.两种新的 MTTP 基因突变在非典型性贝塔脂蛋白血症病例中的分子和功能分析。
J Lipid Res. 2012 Mar;53(3):548-555. doi: 10.1194/jlr.M020024. Epub 2012 Jan 11.
5
Transient infantile hypertriglyceridemia, fatty liver, and hepatic fibrosis caused by mutated GPD1, encoding glycerol-3-phosphate dehydrogenase 1.由突变 GPD1 引起的短暂性婴儿期高甘油三酯血症、脂肪肝和肝纤维化，GPD1 编码甘油-3-磷酸脱氢酶 1。
Am J Hum Genet. 2012 Jan 13;90(1):49-60. doi: 10.1016/j.ajhg.2011.11.028. Epub 2012 Jan 5.
6
Novel mutations of cholesteryl ester transfer protein (CETP) gene in Japanese hyperalphalipoproteinemic subjects.日本人高α脂蛋白血症患者载脂蛋白 CETP 基因的新突变。
Clin Chim Acta. 2012 Mar 22;413(5-6):537-43. doi: 10.1016/j.cca.2011.11.010. Epub 2011 Nov 19.
7
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J Lipid Res. 2011 Dec;52(12):2279-2286. doi: 10.1194/jlr.M019653. Epub 2011 Oct 6.
8
Molecular mechanisms of long noncoding RNAs.长非编码 RNA 的分子机制。
Mol Cell. 2011 Sep 16;43(6):904-14. doi: 10.1016/j.molcel.2011.08.018.
9
Expression of the splicing factor gene SFRS10 is reduced in human obesity and contributes to enhanced lipogenesis.剪接因子基因 SFRS10 的表达在人类肥胖中降低，并有助于增强脂肪生成。
Cell Metab. 2011 Aug 3;14(2):208-18. doi: 10.1016/j.cmet.2011.06.007.
10
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PLoS One. 2011 Apr 29;6(4):e19420. doi: 10.1371/journal.pone.0019420.
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