FIGURE 7.

Several duplex parameters dictate the relative contributions of human RNAi components to guide strand selection. Left: Only Ago2/Dicer/dsRBP complexes are able to efficiently direct strand selection with perfectly matched siRNAs containing identical 5′ nucleotides on both strands or a disfavored 5′ nucleotide on the guide strand. Center: Ago2 alone as well as Dicer/dsRBP-containing complexes are capable of strand selection with duplex RNAs harboring a disfavored 5′ nucleotide on the passenger strand, terminal mismatches, or central mismatches. In certain cases (as with siRNA-3), strand selection by Ago2 may be enhanced above that of Dicer/dsRBP-containing complexes. Right: Ago2 and an Ago2/Dicer/TRBP complexes exhibit robust strand selection with duplex RNAs containing seed mismatches or combined seed and central mismatches, although overall activity is diminished with a TRBP-containing complex (denoted by gray arrow). Strand selection with these RNAs is enhanced by Ago2/Dicer/PACT complexes (denoted by large arrow). Red strand denotes the guide strand. Green highlights the less stable duplex ends.