Vitamin D and alternative splicing of RNA.
Vitamin D and alternative splicing of RNA.
复制标题
维生素 D 和 RNA 的选择性剪接。
DOI：
10.1016/j.jsbmb.2014.09.025
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Hewison,Martin
中科院分区：
文献类型：
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作者：
Zhou,Rui;Chun,ReneF;Lisse,ThomasS;Garcia,AlejandroJ;Xu,Jianzhong;Adams,JohnS;Hewison,Martin
维生素D的活性形式（1α，25-二羟基维生素D，1，25（OH）2D）通过与核高亲和力维生素D受体（VDR）结合发挥其基因组效应。最近对整个基因组中VDR结合位置的深度测序分析显着扩展了我们对维生素D和VDR对基因转录作用的理解。然而，这些研究也促进了对维生素D对基因表达的转录外影响的认识。现在很清楚，维生素D通过影响DNA甲基化、组蛋白乙酰化和microRNA的产生与表观基因组相互作用，以维持正常的生物学功能。也有越来越多的证据表明，维生素D可以影响前mRNA的组成性剪接和选择性剪接，尽管其机制仍不清楚。前mRNA剪接一直被认为是转录后RNA加工事件，但目前的数据表明，这是共转录发生的。已经认识到几种类固醇激素通过募集既可以控制基因转录又可以控制剪接的核受体辅助调节子来协调控制基因转录和前mRNA剪接。目前的审查将讨论这一概念，具体参考维生素D，和异质核核糖核蛋白C（hnRNPC），一个核因子与RNA剪接的既定功能的潜在作用。hnRNPC作为维生素D反应元件结合蛋白（VDRE-BP）参与VDR转录复合物，并可能作为连接VDR指导的基因转录与RNA剪接的偶联因子。通过这种方式，hnRNPC可能提供了一个额外的机制，微调维生素D调节的靶基因expression.This文章的一部分，题为“第17届维生素D研讨会”特刊。
The active form of vitamin D (1α,25-dihydroxyvitamin D, 1,25(OH)2D) exerts its genomic effects via binding to a nuclear high-affinity vitamin D receptor (VDR). Recent deep sequencing analysis of VDR binding locations across the complete genome has significantly expanded our understanding of the actions of vitamin D and VDR on gene transcription. However, these studies have also promoted appreciation of the extra-transcriptional impact of vitamin D on gene expression. It is now clear that vitamin D interacts with the epigenome via effects on DNA methylation, histone acetylation, and microRNA generation to maintain normal biological functions. There is also increasing evidence that vitamin D can influence pre-mRNA constitutive splicing and alternative splicing, although the mechanism for this remains unclear. Pre-mRNA splicing has long been thought to be a post-transcription RNA processing event, but current data indicate that this occurs co-transcriptionally. Several steroid hormones have been recognized to coordinately control gene transcription and pre-mRNA splicing through the recruitment of nuclear receptor co-regulators that can both control gene transcription and splicing. The current review will discuss this concept with specific reference to vitamin D, and the potential role of heterogeneous nuclear ribonucleoprotein C (hnRNPC), a nuclear factor with an established function in RNA splicing. hnRNPC, has been shown to be involved in the VDR transcriptional complex as a vitamin D-response element-binding protein (VDRE-BP), and may act as a coupling factor linking VDR-directed gene transcription with RNA splicing. In this way hnRNPC may provide an additional mechanism for the fine-tuning of vitamin D-regulated target gene expression.This article is part of a Special Issue entitled ‘17th Vitamin D Workshop’.