Elsevier, Developmental Cell, 5(13), p. 605-607, 2007
DOI: 10.1016/j.devcel.2007.10.010
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microRNAs (miRNAs) are noncoding small RNAs of ∼22 nucleotides (nts) that negatively regulate gene expression by binding to the 3′ untranslated region (3′UTR) of messenger RNA transcripts, triggering translational repression or cleavage of the target (reviewed by Bartel, 2004). miRNAs are generally transcribed by RNA polymerase II as primary miRNAs (pri-miRNAs) that range from hundreds to thousands of nts in length and contain one or more extended hairpin structures (reviewed by Du and Zamore, 2005). In animals, the nuclear RNase III enzyme Drosha, collaborating with DGCR8/Pasha/PASH-1, cleaves both strands near the base of the primary stem-loop and yields the precursor miRNA (pre-miRNA), an ∼65-nt stem-loop that harbors the miRNA in the 5′ or 3′ half of the stem (Lee et al., 2003). The cleavage by Drosha defines one end of the mature miRNA and generates a 5′ phosphate and an ∼2-nt 3′ overhang. After being exported to the cytoplasm by Exportin-5/RAN, pre-miRNAs are further cleaved by the RNase III Dicer to define the other end of the mature miRNA and produce the double-stranded miRNA/miRNA∗ duplexes (Du and Zamore, 2005). One strand of the miRNA/miRNA∗ duplex is then preferentially incorporated into the RNA-induced silencing complex (RISC) and can function to negatively regulate target genes (Du and Zamore, 2005).