A Human-specific Mutation Leads to Reduced Interaction Between miR-124a and One of Its Target Genes, PLOD3

MicroRNAs (miRNAs）are a class of noncoding RNAs (20-24 nt) that can post-transcriptionally regulate the expression of protein coding genes in metazoans. Among them, miR-124a, which is preferentially expressed in the brain, controls the neuronal differentiation in mammals. As miRNAs recognize sequences in the 3′ untranslated region (UTR) of the target genes, during human origin, mutations located in the 3′UTRs of the target genes may lead to changes in miRNA regulation. Through target gene prediction and comparative sequence analysis in representative mammalian species, we identified a target gene (PLOD3) of miR-124a, which has a human-specific mutation in the 3′UTR target sequence. Using the in vitro reporter gene system, we discovered that the human specific mutation in the target site of PLOD3 leads to reduced interaction between miR-124a and PLOD3. This result implies that sequence changes located in the 3′UTR segment of the target genes may have functional consequence and eventually contribute to the origin and evolution of human cognition.