Prediction of Mammalian MicroRNA Targets

Benjamin Lewis, Massachusetts Institute of Technology

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MicroRNAs are an abundant class of endogenous ~22 nucleotide RNAs that can play important gene regulatory roles in animals and plants by basepairing to mRNAs to trigger mRNA degradation or repress translation. To predict the targets of mammalian microRNAs, we have developed algorithms that combine thermodynamics-based modeling of RNA:RNA duplex interactions with comparative sequence analysis to identify putative miRNA target sites conserved among multiple species. Comparisons of the sequences of protein-coding genes from related mammalian genomes have uncovered that thousands of mammalian mRNAs have evolved under selective pressure to preserve sites which match the 5' nucleotides of mammalian microRNAs and are supplemented by primary sequence elements. The set of predicted regulatory targets of mammalian microRNAs encompasses a broad range of genes implicated in diverse biological processes. Predicted sites are observed to mediate repression in a HeLa cell reporter system. These findings have provided evidence indicating a broad role for microRNAs in regulating gene expression in mammals.

Abstract Author(s): Benjamin P. Lewis, I-hung Shih, Matthew W. Jones-Rhoades, David P. Bartel, Christopher B. Burge