The primary transcripts of miRNAs, called pri-miRNAs, are transcribed as individual miRNA genes, from introns of protein-coding genes, or from polycistronic transcripts. The RNase Drosha further processes the pri-miRNA into 70–100 nucleotide, hairpin-shaped precursors, called pre-miRNA, which are exported from the nucleus by exportin 5. In the cytoplasm, the pre-miRNA is cleaved by Dicer into an miRNA:miRNA* duplex. Assembled into the RISC, the mature miRNA negatively regulates gene expression by either translational repression or mRNA degradation, which is dependent on sequence complementarity between the miRNA and the target mRNA. ORF, open reading frame.