Structural basis for RISC assembly of human Argonaute2
Zhang et al. report cryo-EM structures of AGO2-siRNA complexes capturing RISC assembly intermediates. They reveal MID-PIWI-mediated duplex loading, α14-guided end sensing, and stepwise passenger peeling. Target RNAs drive passenger ejection, even after cleavage, which supports target-assisted passenger ejection and a bifunctional role of mRNAs in RNAi.
