The miRNA biogenesis pathway. MicroRNAs generated by the canonical pathway are transcribed as precursor RNAs from intergenic, intronic, or polycistronic genomic loci by RNA polymerase II (RNA Pol II/III). The primary miRNA (pri-miRNA) transcript forms a stem-loop structure that is processed by the DGCR8/Drosha complex. The pre-miRNA is exported to the cytoplasm by XPO5, where it is processed into a mature miRNA duplex by Dicer. Finally, the mature miRNA enters into the RISC complex in association with an AGO family member. In the noncanonical pathway, mirtrons, a subset of miRNAs derived from introns, are processed by the spliceosome and the debranching enzyme. In addition to mirtrons, another non-canonical pathway called the simtron pathway involves Drosha but not its partner DGCR8 or Dicer. The mature miRNA produced by these different pathways leads to translational repression or degradation of the target mRNA.
