Figure 3.

RISC assembly pathways and the downstream events in human system. (a) Catalytically active hAGO2 has two pathways dependent on the types of duplex loaded. The cleavage activity is depicted as scissors. This review proposes the existence of an intermediate state named ‘primary RISC (pri‐RISC)’ between the apo and the pre‐RISC. In this state, only the 5′ monophosphate is captured by the MID domain alone while the rest of the duplex is still exposed to solvent. (b) Catalytically inactive (slicer deficient) AGO proteins, hAGO1, hAGO3, and hAGO4, load siRNA and miRNA duplexes. Their RISC assembly is slicer independent regardless of the types of duplex.