How do cells make microRNA?

Cells produce microRNAs (miRNAs) through a multi-step process known as miRNA biogenesis. In transcription, the gene encoding a miRNA is transcribed by RNA polymerase II or RNA polymerase III into a primary miRNA (pri-miRNA) transcript, resulting in precursor molecules. These precursors undergo two cleavage events: one in the nucleus and one in the cytoplasm, to generate mature microRNAs. The pri-miRNA transcript typically contains a hairpin structure. The pri-miRNA transcript is processed in the nucleus by a complex containing the enzyme Drosha and its cofactor DGCR8 (DiGeorge syndrome critical region 8) into a precursor miRNA (pre-miRNA). Drosha cleaves the pri-miRNA near the base of the hairpin structure, releasing the pre-miRNA, which is approximately 70-100 nucleotides in length. The pre-miRNA is then exported from the nucleus to the cytoplasm by Exportin-5, a nuclear export receptor protein. In the cytoplasm, the Dicer complex processes the pre-miRNA into a 20–25-base-pair duplex, comprising the mature miRNA and its reverse complement known as miRNA. This duplex is then delivered to the RNA-induced silencing complex (RISC), which facilitates miRNA-mediated RNA interference in humans. Within the RISC, the mature miRNA serves as a guide sequence for target mRNA recognition. The miRNA-RISC complex then induces gene silencing by inhibiting translation and/or promoting mRNA degradation.