MiRNAs are gene (post-transcriptional) regulators that bind the 3’UTR of target genes.
Single-nucleotide polymorphisms (SNPs) located within a miRNA binding site can impact miRNAdependent
gene regulation by weakening or reinforcing the microRNA:mRNA bond. We present a
general in silico approach enabling researchers to “predict” which of the several SNPs of 3’UTR of
H2AFX gene can mainly affect its regulation. H2AFX gene encodes a member of the H2A histone
family which is central in the detection of and response to DNA double-strand breaks. All the 17
common SNPs located within the 3’UTR of H2AFX gene were analyzed for putative miRNA-binding
sites by using different databases (such as dbSNP and miRBase) and pre-existing algorithms (such as MicroSNiPer and
RNAcofold) in order to calculate the minimum free energies of hybridization of the microRNA:mRNA duplex, for both
the wild-type and mutant alleles. The difference in these energies was also calculated. Since in each tissue one target sequence
can bind only one miRNA at a time, the sum of all the difference of energies can be considered a relevant parameter
for predicting the importance of a SNP with respect to miRNA regulation. We used tertiles to classify the SNPs and
provide a priority list based on their theoretically strongest impact on miRNA binding. By using the described approach,
we provided the basis for a reasoned, user-friendly algorithm-driven selection of SNPs impacting miRNA biology. The
proposed method is helpful for selecting SNPs having a more powerful (putative) biological function, minimizing
workflow and costs for experimental and clinical investigations.
Keywords: 3’UTR, H2AFX, miRNA, prioritization, single-nucleotide polymorphism, SNP.
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