Figure 1.

The microRNA processing pathway. It is postulated that the miRNA processing pathway is linear and universal to all mammalian miRNAs. This process includes the production of the primary miRNA transcript (pri-miRNA) by RNA polymerase II or III and cleavage of the pri-miRNA by the microprocessor complex Drosha–DGCR8 (Pasha) in the nucleus (A). The resulting precursor hairpin, the pre-miRNA, is exported from the nucleus by Exportin-5–Ran-GTP. In the cytoplasm, the RNase Dicer in complex along with RNA-binding cofactor of Dicer complexes known as transactivation response element RNA-binding protein (TRBP) cleaves the pre-miRNA hairpin to its mature length (B). The mature miRNA’s functional strand is loaded together with Argonaute (Ago2) proteins into the RNA-induced silencing complex (RISC), where it guides RISC to silence target mRNAs through mRNA cleavage, translational repression, or deadenylation, whereas the passenger strand is degraded (C).