FIGURE 2.

Canonical miRNA biogenesis and function. miRNA genes are transcribed by RNA Polymerase II (Pol II) and then processed by the sequential action of Drosha and Dicer to liberate the mature miRNA duplex, which is then loaded onto Argonaut proteins (Ago) to form the RNA-induced silencing complex (RISC). As part of the RISC, miRNAs can bind to target mRNAs whereby binding of the miRNA seed sequence is the key requirement for mRNA target recognition. Thus, miRNAs with the same seed sequence are thought to target overlapping sets of mRNAs and are assigned to the same miRNA seed family. miRNA genes can be either monocistronic (miRNA C) or polycistronic (clusters A and B) containing several miRNAs that are usually expressed as one pri-miRNA transcript. Some polycistronic clusters comprise miRNA homologs that have emerged via duplication events (cluster B with miR-B2a, B2b as homologous miRNAs) whereas other clusters consist of miRNAs belonging to different seed families (here exemplarily designated as seed family 1 (in blue) with miRNAs A1, B1, C1, and seed family 2 (in green) with miRNAs A2, B2a, and B2b). For more details on miRNA biogenesis and polycistronic miRNA clusters, see the reviews from Ha and Kim (2014) and Olive et al. (2015), respectively.