The miRNA biogenesis pathway.
Notes: The first step of microRNA biogenesis is the transcription of a long pri-miRNA that contains loop–stem structures. These loop–stem structures will be further cleaved-off, mediated by the Drosha-DGCR8 complex, a processing step that also takes place in the nucleus. The cleavage product is called pre-microRNA and has a typical two nucleotide 3′ overhang, essential for nuclear export by exportin-5. Pre-miRNA constitutes a transport complex together with exportin-5 and its cofactor Ran (the GTP-bound form). Following export, the pre-miRNA is cleaved by Dicer in combination with the TRBP. This yields an approximately 20 base pair miRNA duplex, which is separated and usually one strand is selected as the mature miRNA, whereas the other strand is degraded. After incorporation into miRISC and strand selection, the mature miRNA strand induces translational repression and/or mRNA cleavage, leading to reduction of the protein.18–20
Abbreviations: Ago, argonaute; GTP, guanosine triphosphate; miRISC, miRNA-induced silencing complex; miRNA, microRNA; pri-miRNA, primary miRNA; pre-miRNA, precursor miRNA; TRBP, trans-activation response element RNA binding protein.