Models for efficient and high-fidelity siRNA production by Dicer-2. The phosphate-binding pocket in the Dicer-2 PAZ domain anchors the 5′ monophosphate of long dsRNA. Then C-terminal dsRBD binds the proximal body region of the long dsRNA and aligns the RNA to the RNase III active sites. The distance between the anchoring phosphate-binding pocket and RNase III active sites correspond to 21-nt length, allowing high-fidelity 21-nt siRNA production. In the absence of C-terminal dsRBD, dsRNA is misaligned, resulting in lower-efficiency and lower-fidelity production of siRNAs. In the absence of the phosphate-binding pocket, the RNA terminal end is not properly anchored, resulting in lower-fidelity production of siRNAs. The models align well with the previous structural model of Dicer-2 (Lau et al. 2012).
