@Article{ecn.2010.0218,
AUTHOR = {Susana N. Diniz, Karen P. T. Pendeloski, Andrey Morgun, Iouri Chepelev, Maria Gerbase-DeLima, Natalia Shulzhenko},
TITLE = {Tissue-specific expression of IL-15RA alternative splicing transcripts and its regulation by DNA methylation},
JOURNAL = {European Cytokine Network},
VOLUME = {21},
YEAR = {2010},
NUMBER = {4},
PAGES = {308--318},
URL = {http://www.techscience.com/ECN/v21n4/65850},
ISSN = {1952-4005},
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.},
DOI = {10.1684/ecn.2010.0218}
}