In silico analysis of microRNAS targeting the HLA-G 3′ untranslated region alleles and haplotypes

• Published in: Human immunology 2009-12, Vol.70 (12), p.1020-1025
• Main Authors: Castelli, Erick C, Moreau, Philippe, Chiromatzo, Alynne Oya e, Mendes-Junior, Celso Teixeira, Veiga-Castelli, Luciana C, Yaghi, Layale, Giuliatti, Silvana, Carosella, Edgardo D, Donadi, Eduardo Antonio
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; 3′ untranslated region; Alleles; Allergy and Immunology; Base Sequence; Binding Sites; Computational Biology; Gene Expression Regulation; Haplotype; Haplotypes; Histocompatibility Antigens Class I - genetics; HLA Antigens - genetics; HLA-G; HLA-G Antigens; Humans; MicroRNA; MicroRNAs - genetics; MicroRNAs - physiology; Molecular Sequence Data; Polymorphism, Single Nucleotide
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2009.07.028

Abstract It has been reported that microRNAs (miRNA) may have allele-specific targeting for the 3′ untranslated region (3′ UTR) of the HLA-G locus. In a previous study, we reported 11 3′UTR haplotypes encompassing the 14-bp insertion/deletion polymorphism and seven SNPs (+3003 T/C, +3010 C/G, +3027 C/A, +3035 C/T, +3142 C/G, +3187 A/G, and +3196 C/G), of which only the +3142 C/G SNP has been reported to influence the binding of miRNAs. Using bioinformatics analyses, we identified putative miRNA-binding sites considering the haplotypes encompassing these eight polymorphic sites, and we ranked the lowest free energies that could potentially lead to an mRNA degradation or translational repression. When a specific haplotype or a particular SNP was associated with a miRNA-binding site, we defined a free energy difference of 4 kcal/mol between alleles to classify them energetically distant. The best results were obtained for the miR-513a-5p, miR-518c*, miR-1262 and miR-92a-1*, miR-92a-2*, miR-661, miR-1224-5p, and miR-433 miRNAs, all influencing one or more of the +3003, +3010, +3027, and +3035 SNPs. The miR-2110, miR-93, miR-508-5p, miR-331-5p, miR-616, miR-513b, and miR-589* miRNAs targeted the 14-bp fragment region, and miR-148a, miR-19a*, miR-152, mir-148b, and miR-218-2 also influenced the +3142 C/G polymorphism. These results suggest that these miRNAs might play a relevant role on the HLA-G expression pattern.