Identification of MicroRNA Regulatory Targets in Vertebrates

Benjamin Lewis, Massachusetts Institute of Technology

By analyzing the evolution of vertebrate genes, we have identified microRNA regulatory targets. MicroRNA target sites are complementarity to the seed (nucleotides 2-7) of the miRNA and are generally preserved in vertebrate evolution at a significantly higher rate than comparable sequences. An overrepresentation of conserved adenosines flanking the seed complementary sites in target mRNAs indicates that primary sequence determinants can supplement base pairing to specify miRNA target recognition. In a four-genome analysis, almost 14,000 regulatory relationships were detected above the estimate of the false-positive predictions, thereby implicating as miRNA targets more than 6000 human genes, which represented approximately one third of our starting set. Extrapolating this result to all genes in the human genome, we infer that over one third of human genes are likely to be conserved microRNA targets, thus underscoring the wide breadth and importance of regulation by microRNAs in vertebrates.

Abstract Author(s): Benjamin Lewis