The microRNA biogenesis pathway. The canonical biogenesis pathway starts in the nucleus by cleavage of the pri-miRNA transcript by the Drosha-DGCR8 microprocessor complex . After nuclear processing, the resulting precursor hairpin (pre-miRNA) is transported into the cytoplasm by Exportin-5 in complex with Ran-GTP . In the cytoplasm, cleavage into an approximately 22-nucleotide duplex is achieved by the RNase III Dicer  and its interactors TRBP and PACT [131,132]. To form the active RNA-induced silencing complex (RISC) that performs gene silencing, the functional guide strand has to be separated from the passenger strand, which is degraded subsequently . miRNA, microRNA.