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

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

Author Diniz, Susana N. Autor UNIFESP Google Scholar
Pendeloski, Karen P. T. Autor UNIFESP Google Scholar
Morgun, Andrey Autor UNIFESP Google Scholar
Chepelev, Iouri Google Scholar
Gerbase-DeLima, Maria Autor UNIFESP Google Scholar
Shulzhenko, Natalia Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
NIAID
NHLBI
Abstract The human IL-15RA gene encoding the alpha chain of the IL-15 receptor is expressed in a variety of immune and non-immune cell types from different tissues, and generates multiple splicing events of functional importance. We aimed to evaluate expression of IL-15RA transcripts generated by alternative usage of transcription start site (Var1 and Var2) and by deletion of exon 3 (Del3), exon 2 (Del2), or both (Del2,3) in different human tissues. Since a CpG island was found near to the IL-15RA gene transcription start site, we also investigated the role of DNA methylation on the expression of IL-15RA full-length and alternative transcripts fragments in peripheral blood mononuclear cells (PBMC). IL-15RA transcription of functional (full-length and del 3) and non-functional (del 2 and del 2,3) variants was detected in many tissues, however, the number of different 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. However, 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 in the tissues investigated. When PBMC cultures were treated with 5-azacitidine (AZA), a DNA methyltransferase inhibitor, we detected a significant increase in IL-15RA copy number. Only alternative exon skipping events of Var1 (Del 2, Del 3 and Del 2, 3) were altered by AZA treatment, which is consistent with the CpG island localization 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 regulatory role of DNA methylation in IL-15RA transcript Var1 expression in mononuclear cells.
Keywords IL-15RA
alternative splicing
DNA methylation
5-azacitidine
Language English
Sponsor AFIP (Associacao Fundo de Incentivo a Psicofarmacologia)
Date 2010-12-01
Published in European Cytokine Network. Montrouge: John Libbey Eurotext Ltd, v. 21, n. 4, p. 308-318, 2010.
ISSN 1148-5493 (Sherpa/Romeo, impact factor)
Publisher John Libbey Eurotext Ltd
Extent 308-318
Origin http://www.jle.com/en/revues/ecn/e-docs/tissue_specific_expression_of_il_15ra_alternative_splicing_transcripts_and_its_regulation_by_dna_methylation_286787/article.phtml
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000285408800012
URI http://repositorio.unifesp.br/handle/11600/33101

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