microRNAs targeting the immunomodulatory HLA-G gene: A new survey searching for microRNAs with potential to regulate HLA-G

Author(s)

Porto, Iane O. P. ^[1] ; Mendes-Junior, Celso T. ^[2] ; Felicio, Leandro P. ^[3] ; Georg, Raphaela C. ^[3] ; Moreau, Philippe ^{[4, 5]} ; Donadi, Eduardo A. ^[6] ; Bogo Chies, Jose Artur ^[7] ; Castelli, Erick C. ^[1]

Affiliation

^[1] UNESP Univ Estadual Paulista, Fac Med Botucatu, Dept Patol, Botucatu, SP - Brazil

^[2] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, BR-14049 Ribeirao Preto, SP - Brazil

^[3] Univ Fed Goias, Inst Ciencias Biol, Goiania, Go - Brazil

^[4] Hop St Louis, Serv Rech Hematoimmunol, Inst Malad Emergentes & Therapies Innovantes, Commissariat Energie Atom & Energies Alternat, Paris - France

^[5] Univ Paris Diderot, Hop St Louis, Sorbonne Paris Cite, Inst Univ Hematol, UMR E5, Paris - France

^[6] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Clin Med, Div Imunol Clin, BR-14049 Ribeirao Preto, SP - Brazil

^[7] Univ Fed Rio Grande do Sul, Dept Genet, Porto Alegre, RS - Brazil

• Document type: Journal article
• Source: Molecular Immunology; v. 65, n. 2, p. 230-241, JUN 2015.
• Web of Science Citations: 34

Abstract

The HLA-G gene is a non-classical class I MHC, responsible for modulating immune responses by inhibiting Natural Killer and cytotoxic T cells, presenting a crucial role in maternal tolerance to the fetus. In non-pathological conditions, its expression is restricted to certain tissues such as cornea and placenta. The HLA-G 3 ` untranslated region (3 ` UTR) has been reported to play an important role in the control of mRNA and protein levels, and polymorphisms in this region may influence mRNA stability and microRNA binding. In this study, we propose an approach to detect and classify microRNAs regarding their ability to bind the target (in this case, HLA-G 3 ` UTR) and the specificity of such interactions. Then, a panel of microRNAs with potential to modulate HLA-G expression is proposed, in which some microRNAs, such as miR-139-3p, would bind to non-polymorphic sequences of the HLA-G 3 ` UTR in a stable and specific manner, while others, such as miR-608, binds to polymorphic sequences and therefore the binding might be influenced by the variant actually present. Additionally, both HLA-G 3 ` UTR polymorphisms and the microRNA microenvironment must be considered when studies correlating HLA-G expression profiles and polymorphisms are being conducted. These new data may provide a remarkable contribution to the understanding of the mechanisms underlying HLA-G post-transcriptional regulation, disclosing the impact of variable and non-variable regions on HLA-G biology and providing a unique microRNA repertoire for future functional studies and therapeutic use. (C) 2015 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 13/17084-2 - Evaluation of MHC Class I genes variability, regulation and evolutive history
• Grantee: Erick da Cruz Castelli
• Support Opportunities: Regular Research Grants