Computational Assessment of miRNA Binding to Low and High Expression HLA-DPB1 Allelic Sequences.

Cell surface expression of HLA-DP is allele specific. SNP rs9277534 (A/G), located in the 3'UTR of the DPB1 gene, has been associated with either low (A) or high (G) expression of DP on the cell surface. Considering the role of miRNAs in the regulation of gene expression, we computationally identified the miRNAs of two BLCLs, PGF and COX, predicted to interact with their corresponding DPB1 transcripts, DPB1∗04:01:01:01-low expression and DPB1∗03:01:01:01-high expression. The identified target sequences are located primarily in intron 2 and the 3'UTR. We hypothesize that gene expression may be influenced first by nuclear pre-mRNA events involving intronic regions, followed by the usual 3'UTR-associated events in the cytoplasm. The low DP expression allele was found to interact in silico with a larger number of miRNAs than the high expression allele. This pattern holds when examining either the entire transcript unit or simply the polymorphic sites that differentiate the alleles. Interestingly, the rs9277534 A/G polymorphism appears to be in linkage disequilibrium with polymorphisms targeted by the identified miRNAs. The multiplicity of sites targeted by different miRNAs suggests that the expression of DPB1 may be a dynamic process, influenced by different miRNAs under different states of the cell.