Fig. 8: Model of structured RNA processing by Dis3L2.

RNA-free Dis3L2 is preorganized in a vase conformation to bind RNA substrates (yellow), with a seven-nucleotide-deep tunnel leading to the nuclease active site. When the RNA overhang is shortened to ~12 nucleotides, additional contacts are made to the dsRNA. Further shortening of the overhang triggers a large rearrangement of the two CSD domains (pink and orange) to the prong conformation and allows the base of the dsRNA to access a module in the RNB domain (blue) that acts as a wedge to separate the two RNA strands and allows entry of one of the strands into the narrow tunnel leading to the active site. In this way, the enzyme ensures continued RNA degradation during RNA duplex unwinding.