MicroRNAs (miRNAs), a class of ∼21–23 nucleotide long non-coding RNAs (ncRNAs), have critical roles in diverse biological processes that encompass development, proliferation, apoptosis, stress response, and fat metabolism. miRNAs recognize their target mRNA transcripts by partial sequence complementarity and collectively have been estimated to regulate the majority of human genes. Consequently, misregulation of miRNAs or disruption of their target sites in genes has been implicated in a variety of human diseases ranging from cancer metastasis to neurological disorders. With the development and availability of genomic technologies and computational approaches, the field of miRNA biology has advanced tremendously over the last decade. Here we review the genome-wide approaches that have allowed for the discovery of new miRNAs, the characterization of their targets, and a systems-level view of their impact. WIREs Syst Biol Med 2011 3 491–512 DOI: 10.1002/wsbm.128

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