How are microRNAs made inside the cell?

MicroRNA biogenesis follows a multi-step pathway. First, miRNA genes are transcribed in the nucleus by RNA polymerase II to produce a long primary transcript called pri-miRNA. The enzyme DROSHA then cleaves this into a shorter stem-loop structure called pre-miRNA (approximately 60–70 nucleotides). The pre-miRNA is exported from the nucleus to the cytoplasm by Exportin-5. In the cytoplasm, the enzyme DICER cleaves the stem-loop into a short double-stranded RNA duplex. One strand (the guide strand, which becomes the mature miRNA) is loaded into the RNA-induced silencing complex (RISC), while the other strand is degraded. The RISC-miRNA complex then scans mRNA molecules for complementary sequences and silences them. Cancer cells often have disruptions in this biogenesis pathway, causing specific miRNAs to be over- or underproduced.