title: Vitamin D and alternative splicing of RNA.
abstract: 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'.
authors.affiliation: UCLA Orthopaedic Hospital, Department of Orthopaedic Surgery, Orthopaedic Hospital, University of California at Los Angeles, Los Angeles, CA 90095, USA; Department of Orthopaedics, the Orthopedic Surgery Center of Chinese PLA, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.affiliation: UCLA Orthopaedic Hospital, Department of Orthopaedic Surgery, Orthopaedic Hospital, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Rene F
authors.initials: RF
authors.lastname: Chun
authors.affiliation: Mount Desert Island Biological Laboratory, 159 Old Bar Harbor Road, Salisbury Cove, ME 04672, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Lisse
authors.affiliation: UCLA Orthopaedic Hospital, Department of Orthopaedic Surgery, Orthopaedic Hospital, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Alejandro J
authors.initials: AJ
authors.lastname: Garcia
authors.affiliation: Department of Orthopaedics, the Orthopedic Surgery Center of Chinese PLA, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Xu
authors.affiliation: UCLA Orthopaedic Hospital, Department of Orthopaedic Surgery, Orthopaedic Hospital, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Adams
authors.affiliation: UCLA Orthopaedic Hospital, Department of Orthopaedic Surgery, Orthopaedic Hospital, University of California at Los Angeles, Los Angeles, CA 90095, USA. Electronic address: mhewison@mednet.ucla.edu.
authors.forename: Martin
authors.initials: M
authors.lastname: Hewison
mesh_terms: D017398:Alternative Splicing / Q000187:drug effects* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D012313:RNA / Q000187:drug effects* / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics*; D014807:Vitamin D / Q000494:pharmacology*; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D018167:Receptors, Calcitriol; D014815:Vitamins; D014807:Vitamin D; D012313:RNA
keywords: Heterogenous nuclear ribonucleoprotein C; RNA; Splicing; Transcription; Vitamin D