title: MicroRNAs targeting the immunomodulatory HLA-G gene: a new survey searching for microRNAs with potential to regulate HLA-G.
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.
authors.affiliation: Departamento de Patologia, Faculdade de Medicina de Botucatu, UNESP - Univ. Estadual Paulista, Botucatu, SP, Brazil.
authors.forename: Iane O P
authors.initials: IO
authors.lastname: Porto
authors.affiliation: Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Celso T
authors.initials: CT
authors.lastname: Mendes-Junior
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Brazil.
authors.forename: Leandro P
authors.initials: LP
authors.lastname: Felício
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Brazil.
authors.forename: Raphaela C
authors.initials: RC
authors.lastname: Georg
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives, Institut des Maladies Emergentes et des Thérapies Innovantes, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, Paris, France; Université Paris-Diderot, Sorbonne Paris-Cité, UMR E5, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.affiliation: Divisão de Imunologia Clínica, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Donadi
authors.affiliation: Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: José Artur Bogo
authors.initials: JA
authors.lastname: Chies
authors.affiliation: Departamento de Patologia, Faculdade de Medicina de Botucatu, UNESP - Univ. Estadual Paulista, Botucatu, SP, Brazil. Electronic address: castelli@fmb.unesp.br.
authors.forename: Erick C
authors.initials: EC
authors.lastname: Castelli
mesh_terms: D020413:3' Untranslated Regions / Q000502:physiology*; D030561:Databases, Nucleic Acid; D005786:Gene Expression Regulation / Q000502:physiology*; D059951:HLA-G Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D056747:Immunomodulation / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D011110:Polymorphism, Genetic / Q000276:immunology; D020871:RNA Stability / Q000502:physiology
chemical_list: D020413:3' Untranslated Regions; D059951:HLA-G Antigens; C555098:MIRN139 microRNA, human; C000591804:MIRN608 microRNA, human; D035683:MicroRNAs
keywords: 3′ untranslated region (3′UTR); Expression regulation; HLA-G; Polymorphisms; Post-transcriptional regulation; microRNA