| PubMed Abstract |
MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression in plants and animals. Although their biological
importance has become clear, how they recognize and regulate target genes remains less well understood. Here, we systematically
evaluate the minimal requirements for functional miRNA-target duplexes in vivo and distinguish classes of target sites with
different functional properties. Target sites can be grouped into two broad categories. 5' dominant sites have sufficient
complementarity to the miRNA 5' end to function with little or no support from pairing to the miRNA 3' end. Indeed, sites
with 3' pairing below the random noise level are functional given a strong 5' end. In contrast, 3' compensatory sites have
insufficient 5' pairing and require strong 3' pairing for function. We present examples and genome-wide statistical support
to show that both classes of sites are used in biologically relevant genes. We provide evidence that an average miRNA has
approximately 100 target sites, indicating that miRNAs regulate a large fraction of protein-coding genes and that miRNA 3'
ends are key determinants of target specificity within miRNA families.
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