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

Erick C Castelli, Philippe Moreau, Alynne Oya e Chiromatzo, Celso Teixeira Mendes-Junior, Luciana C Veiga-Castelli, Layale Yaghi, Silvana Giuliatti, Edgardo D Carosella, Eduardo Antonio Donadi
Human Immunology 2009, 70 (12): 1020-5
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.

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