Abstract
RNA-dependent RNA polymerases (RdRps) of the segmented double-stranded (ds) RNA viruses of the Reoviridae family exhibit distinguishing structural elements, enabling the enzymes to function within the confines of a proteinaceous core particle. These globular, cage-like polymerases are traversed by four well-defined tunnels, which not only allow template RNAs, nucleotides, and divalent cations to access the interior catalytic site, but also provide two distinct exit conduits for RNA templates and products--one leading out of the core and the other back inside the core. Although Reoviridae RdRps are intrinsically capable of binding template, their catalytic activities are tightly regulated by interactions with core shell proteins. This intra-particle mechanism of RNA synthesis coordinates genome packaging with replication during the infectious cycle.