miRNA biogenesis and action. Most pri-mRNAs are the products of independent genes, transcribed by RNA polymerase II. The nuclear Microprocessor protein complex, which contains the RNase III Drosha and its partner DGCR8/Pasha, cleaves pri-miRNAs into 50- to 80-base pre-miRNA stem-loop moieties. The Ran-GTP–dependent factor exportin-5 actively transports pre-miRNAs into the cytoplasm, where the nuclease Dicer processes them further into duplexes that contain the 20- to 24-nucleotide mature miRNA; each pre-miRNA usually yields a single mature miRNA product. The functional strand is determined when one of the 2 strands of the duplex is loaded into the RISC, which contains Argonaute and related proteins and localizes in cytoplasmic P-bodies. Recognition of target mRNAs by partial sequence complementarity to the miRNA results in posttranscriptional gene repression by some combination of transcript degradation and translational inhibition.