Fig. 1.

Schematic of the canonical and non-canonical pathways of microRNA (miRNA) biogenesis. Canonical pathway is carried out by 6 steps as follows: 1. miRNA transcription by polymerase II 2. Pri-miRNA cleavage by microprocessors 3. Export of pre-miRNA by Exportin 5 4. Pre-miRNA cleavage by Dicer 5. Guide strand forms a miRNA-induced silencing complex (miRISC) after attachment to AGO 6. Binding of miRISC to target mRNA or export to other cells in extracellular vesicles. Several non-canonical pathways exist, for example beginning with transcription of the miRtrons followed by splicing by debranching enzyme 1 (DBR1) resulting in pre-miRNA that then follows the export as and final cleavage per the canonical pathway steps 3–6