Sequence specificity for uridylylation of the viral peptide linked to the genome (VPg) of enteroviruses

Enteroviruses (EV) uridylylate a peptide, VPg, as the first step in their replication. VPgpUpU, found free in infected cells, serves as the primer for RNA elongation. The abilities of four polymerases (3D^pol), from EV-species A-C, to uridylylate VPgs that varied by up to 60% of their residues were compared. Each 3D^pol was able to uridylylate all five VPgs using polyA RNA as template, while showing specificity for its own genome encoded peptide. All 3D^pol uridylylated a consensus VPg representing the physical chemical properties of 31 different VPgs. Thus the residues required for uridylylation and the enzymatic mechanism must be similar in diverse EV. As VPg-binding sites differ in co-crystal structures, the reaction is probably done by a second 3D^pol molecule. The conservation of polymerase residues whose mutation reduces uridylylation but not RNA elongation is compared.