miRNA biogenesis and examples of post-transcriptional controls. MiRNAs are transcribed as pri-miRNAs by RNA polymerase II and processed by the endonuclease Drosha/DGCR8 to a shorter pre-miRNA hairpin structure. The pre-miRNA is exported to the cytoplasm by the Exportin-5–Ran-GTP and cleaved by DICER/TRBP complex to generate the mature length of the miRNA structure. One strand of the miRNA duplex, the guide strand, is then loaded with Argonaute (Ago2) proteins into the RNA-induced silencing complex (RISC), where it guides RISC to silence target mRNAs through mRNA cleavage or translational repression. Beyond this well described linear miRNA processing pathway, miRNA biogenesis is also subject to complex post-transcriptional controls. Some are indicated by the arrows in the figure. These include RNA editing of the pri-miRNA structure (blue arrow), regulation of miRNA biogenesis partners (red arrows), trafficking to P-bodies and polyuridylation for miRNA stability, cytosolic abundance and Dicer processing. Reprinted and adapted with permission from [4].