Schematic representation of miRNA (miR) biogenesis. A, Most miRs are transcribed as polycistronic primary-miRs (pri-miRs) by RNA polymerase II, before undergoing 5' capping and 3' polyadenylation. Portions of the pri-miR folds back on itself to form double-stranded stem-loop structures. B, The Microprocessor complex cleaves these stem-loops from pri-miRs, generating 50–70 bp pre-miRs with a short 3' overhang. Drosha and DGCR8 are the obligate components of the Microprocessor complex, though additional accessory proteins, such as the RNA helicases P68 and P72, can regulate the activity of the complex. C, The short 3' overhang is recognized by components of the nuclear export machinery, leading to active transport of pre-miRs out into the cytosol. In the cytosol, Dicer acts in complex with accessory proteins to process the pre-miRs into double stranded 22 bp duplexes. D, Dicer then assists in loading one strand of this duplex, the guide strand, into the Argonaute-containing RISC complex. E, Mature miRs guide the RISC complex to specific mRNA targets. miRs identify mRNA targets through regions of sequence homology in the mRNA's 3' UTR. The outcome of this interaction can depend on the degree of sequence complementarity and the specific Argonaute present in the RISC complex, but destabilization of the mRNA and subsequent degradation is likely.