In silico analysis of microRNAS targeting the HLA-G 3' untranslated region alleles and haplotypes.
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.
Castelli
Erick C
EC
Division of Clinical Immunology, Department of Medicine, School of Medicine of Ribeirao Preto, University of São Paulo, São Paulo, Brazil. erick.castelli@gmail.com
Moreau
Philippe
P
Oya e Chiromatzo
Alynne
A
Mendes-Junior
Celso Teixeira
CT
Veiga-Castelli
Luciana C
LC
Yaghi
Layale
L
Giuliatti
Silvana
S
Carosella
Edgardo D
ED
Donadi
Eduardo Antonio
EA
D020413:3' Untranslated Regions / Q000235:genetics*; D000483:Alleles; D001483:Base Sequence; D001665:Binding Sites; D019295:Computational Biology; D005786:Gene Expression Regulation; D006680:HLA Antigens / Q000235:genetics*; D059951:HLA-G Antigens; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide
D020413:3' Untranslated Regions; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D035683:MicroRNAs