N- and RNA-facilitated panhandle formation, specific recognition of the vRNA panhandle by N, and N-mediated panhandle dissociation. (A) vRNA synthesis results in an initial RNA with termini that are not base-paired and with associated N in the form of a nucleocapsid. Within the nucleocapsid there is both N–RNA interaction as well as intermolecular association between individual N trimers. (B) The RNA chaperone activity of N, in conjunction with the low P-num nucleotides that comprise the termini, facilitates panhandle formation. N that is intrinsically associated with the nucleocapsid or, alternatively, free N might mediate panhandle formation. (C) Following panhandle formation, N protein binds in a structure-specific manner, with high affinity, to the panhandle. In the figure the trimeric N that is stably bound to the panhandle is depicted in darker shading than the other associated N molecules simply for emphasis. (D) N protein mediates the unwinding of the panhandle and remains associated with the nucleotides at the 5′ end of the molecule. (E) Dissociation of the panhandle likely enables initiation of replication mediated by the viral RNA dependent RNA polymerase (RdRp). In the figure, N, which is bound to the 5′ end of the panhandle, is shown in association with the RdRp. This association is hypothetical.
