Extended Data Fig. 8: A working model for the long RNA processing and 21-nt siRNA biogenesis by the DCL4-DRB4 complex.
a, A proposed model illustrating DRB4’s role in assisting DCL4 with long dsRNA processing. The DRB4CTD-DCL4dsRBD2 interaction may position the DRB4dsRBD1/2 (modeled from PDB: 2N3F) to a distal position of the dsRNA, achieving the long RNA substrate preference of the DCL4-DRB4 complex. b, A working model of the long RNA processing by the DCL4-DRB4 complex to produce phasiRNA by continuously dicing. The red arrow and stars indicate the direction of RNA translocation and the cleavage site, respectively. The DRB4dsRBD1/2 may help DCL4 search and capture long RNA substrates. Once the RNA is bound by the DCL4-DRB4 complex, DCL4 helicase domain could pump the RNA towards the platform-PAZ domain cassette, resulting in RNA bending. Upon the platform-PAZ domain cassette capturing the RNA termini, the pumping may push the RNA to further bend to approach the catalytic center of DCL4 RIIIs for cleavage. After cleavage, the 21-nt siRNA duplex is released, and the remaining RNA fragment, which is held by the helicase domain, could further be pumped by the helicase to start the next dicing cycle.
