One of the most exciting recent developments in RNA biology has been the 
discovery of small non-coding RNAs that affect gene expression through the RNA 
interference (RNAi) mechanism. Two major classes of RNAs involved in RNAi are 
small interfering RNA (siRNA) and microRNA (miRNA). Dicer, an RNase III enzyme, 
plays a central role in the RNAi pathway by cleaving precursors of both of these 
classes of RNAs to form mature siRNAs and miRNAs, which are then loaded into the 
RNA-induced silencing complex (RISC). miRNA and siRNA precursors are quite 
structurally distinct; miRNA precursors are short, imperfect hairpins while 
siRNA precursors are long, perfect duplexes. Nonetheless, Dicer is able to 
process both. Dicer, like the majority of RNase III enzymes, contains a dsRNA 
binding domain (dsRBD), but the data are sparse on the exact role this domain 
plays in the mechanism of Dicer binding and cleavage. To further explore the 
role of human Dicer-dsRBD in the RNAi pathway, we determined its binding 
affinity to various RNAs modeling both miRNA and siRNA precursors. Our study 
shows that Dicer-dsRBD is an avid binder of dsRNA, but its binding is only 
minimally influenced by a single-stranded - double-stranded junction caused by 
large terminal loops observed in miRNA precursors. Thus, the Dicer-dsRBD 
contributes directly to substrate binding but not to the mechanism of 
differentiating between pre-miRNA and pre-siRNA. In addition, NMR spin 
relaxation and MD simulations provide an overview of the role that dynamics 
contribute to the binding mechanism. We compare this current study with our 
previous studies of the dsRBDs from Drosha and DGCR8 to give a dynamic profile 
of dsRBDs in their apo-state and a mechanistic view of dsRNA binding by dsRBDs 
in general.