Figure 2. The RNAi pathway. MicroRNAs are transcribed in the nucleus as precursor pri-miRNAs, which form hairpins that are processed to mature miRNAs by two RNase III enzymes, drosha and dicer. [a(1)] The pre-miRNA product produced by drosha cleavage is exported to the cytoplasm, where dicer processes it to a duplex of 20-25 nucleotides. [b] One strand of the duplex is incorporated into the RNA-induced silencing complex (RISC). The miRNA recognizes target mRNAs by the complementary base pairing. [c] Perfect complementarity leads to cleavage of the target mRNA. [a(2)] Small interfering RNAs enter the pathway in the cytoplasm, just upstream of the RNA loading into RISC. siRNA and miRNA companies have adopted different strategies to use this same pathway to achieve therapeutic outcomes. The major mechanism or step at which companies intervene in the RNAi pathway is indicated.