Vitamin D and alternative splicing of RNA. Issue 148 (April 2015)

• Record Type: Journal Article
• Authors: Zhou, Rui; Chun, Rene F.; Lisse, Thomas S.; Garcia, Alejandro J.; Xu, Jianzhong; Adams, John S.; Hewison, Martin
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 148(2015)
• Page Start: 310
• Page End: 317
• Publication Date: 2015-04
• Subjects: Vitamin D -- RNA -- Transcription -- Splicing -- Heterogenous nuclear ribonucleoprotein C; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2014.09.025
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: Vitamin D receptor (VDR) signaling influences both genetic and epigenetic responses. VDR responses may also be mediated via effects on RNA splicing. Heterogenous nuclear ribonucleoprotein C1/C2 (hnRNPC1/C2) is a known component of RNA processing. HnRNPC1/C2 also interacts with DNA where it functions as a vitamin D response element binding protein (VDRE-BP). HnRNPC1/C2 may play a role in bridging VDR-mediated transcription and effects on RNA splicing. Abstract: The active form of vitamin D (1α, 25-dihydroxyvitamin D, 1, 25(OH)2 D) 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'.