Loquacious-PD regulates the terminus-dependent molecular recognition of Dicer-2 toward double-stranded RNA.

Dicer-2 cleaves double-stranded RNA into siRNAs in a terminus-dependent manner as part of D. melanogaster's RNA interference pathway. Using ultrafast fluorescence, we probe the local environment of chromophores at the dsRNA terminus upon binding by Dicer-2 and interrogate the effects of Loquacious-PD, an accessory protein. We find substrate-selective modes of molecular recognition that distinguish between blunt and 3'overhang termini, but whose differences are greatly reduced by Loquacious-PD. These results connect the molecular recognition properties of Dicer-2 to its selective processing of dsRNAs with different termini and to its need for Loquacious-PD to efficiently produce endogenous siRNAs.