Defining miRNA Targets: Balancing Simplicity with Complexity
Micro RNAs (miRNAs) are small RNAs that play an important role in the negative regulation of gene expression by suppressing protein translation. Animal genomes contain an abundance of small genes that produce regulatory RNAs of about 22 nucleotides in length. The Ambros lab identified the first miRNAs in 1993 while characterizing a genetic locus involved in the control of developmental timing in C. elegans.1 It has since been shown that these miRNAs are diverse in sequence and expression patterns and are evolutionarily widespread, suggesting that they may participate in a wide range of genetic and regulatory pathways. Since their initial discovery, thousands of papers have been published characterizing miRNA properties, defining their expression, and demonstrating function. MiRNAs are initially transcribed as long primary miRNAs (pri-miRNAs) that are processed by the RNase III enzyme Drosha to generate stem-loop precursor miRNAs (pre-miRNAs) approximately 70 nucleotides in length.2 These precursors are exported into the cytoplasm and, subsequently, the cytoplasmic enzyme Dicer cleaves the pre-miRNA to release the mature miRNA.3 Binding of miRNA to a messenger RNA (mRNA) with Ago proteins inhibits protein translation. It is estimated that the human genome encodes about 1500 miRNAs that are thought to regulate more than 30% of protein-coding genes.4 As interindividual variation of miRNA expression levels influences the expression of a myriad of miRNA target genes; these processes likely contribute to phenotypic differences and susceptibility to common and complex disorders.
- Received April 24, 2013.
- Accepted April 25, 2013.