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Simplified schematic of RNAi in mammalian cells. RNAi in mammalian cells is primarily mediated by endogenous miRNAs. miRNAs are expressed as primary hairpin-containing transcripts that are processed in the nucleus and cytoplasm to yield mature miRNA duplexes of ~22 nt in length. A single strand of the duplex is then loaded into an argonaute-containing silencing complex (RISC), which then guides the complex to target mRNA transcripts with partial sequence complementarity within their 3’UTRs. This interaction leads to degradation and/or translational repression.