Open Access

ARTICLE

Tissue-specific expression of IL-15RA alternative splicing transcripts and its regulation by DNA methylation

Susana N. Diniz^1,2, Karen P. T. Pendeloski¹, Andrey Morgun^1,3, Iouri Chepelev⁴, Maria Gerbase-DeLima^1,*, Natalia Shulzhenko^1,3,*

1 Immunogenetic division, Federal University of São Paulo (UNIFESP), São Paulo (SP), Brazil
2 Departament of Pharmacy, Bandeirante University of São Paulo (UNIBAN), SP, Brazil
3 “Ghost lab”, Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA
4 Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA

* Corresponding Author: S.N. Diniz,

European Cytokine Network 2010, 21(4), 308-318. https://doi.org/10.1684/ecn.2010.0218

Accepted 10 September 2010;

Abstract

The human IL-15RA gene encoding the alpha chain of the IL-15 receptor is expressed in a varietyof immune and non-immune cell types from different tissues, and generates multiple splicing events of func-tional importance. We aimed to evaluate expression of IL-15RA transcripts generated by alternative usage oftranscription start site (Var1 and Var2) and by deletion of exon 3 (Del3), exon 2 (Del2), or both (Del2,3) in dif-ferent human tissues. Since a CpG island was found near to the IL-15RA gene transcription start site, we alsoinvestigated the role of DNA methylation on the expression of IL-15RA full-length and alternative transcriptsfragments in peripheral blood mononuclear cells (PBMC). IL-15RA transcription of functional (full-length anddel 3) and non-functional (del 2 and del 2,3) variants was detected in many tissues, however, the number ofdifferent IL-15RA transcripts variants detected in each tissue did not correlate with the level of gene expression.IL-15RA transcript variants Var1 and Var2 presented similar expression levels in different human tissues. How-ever, we found a distinct expression profile of functional and non-functional IL-15RA transcripts fragments.A preferential expression of transcripts that bind IL-15 compared to IL-15 non-binding transcripts was seen inthe tissues investigated. When PBMC cultures were treated with 5-azacitidine (AZA), a DNA methyltransferaseinhibitor, we detected a significant increase in IL-15RA copy number. Only alternative exon skipping events ofVar1 (Del 2, Del 3 and Del 2, 3) were altered by AZA treatment, which is consistent with the CpG island locali-zation in the regulatory region 5’ upstream of the transcription start site of Var1 and not of Var2. Therefore,this work shows a broad expression pattern of functional IL-15RA splicing forms and suggests a regulatoryrole of DNA methylation in IL-15RA transcript Var1 expression in mononuclear cells.

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