Mode 1: Both RBD3 and RBD4 form the RNA-protein interaction interface
In mode 1 scenario, the interface is built by the contribution of RBD3 with conserved residues on the RNP1 motif (K217, Y219, F221) as well as new interacting residues identified in RBD4 (positively charged residues on β-2 strand (R291, R293)) and on the linker loop between β-2 and β-3 (R298). This binding mode is predicted for the interactions of mir-16, mir-221, and mir-222 with NCL. In this putative binding mode, RBD3 and RBD4 interact with the double stranded RNA from opposite ends and cooperate to hold the miRNA molecule in a clasped orientation (Fig 3 ).