Formation and working mechanism of the picornavirus VPg uridylylation complex

•VPg uridylylation is a featured process in the initiation of picornavirus replication.•Viral proteins and RNA elements are involved in the VPg uridylylation complex.•Picornaviral VPgs bind viral RdRp with high diversity.•Current knowledge provides snapshots regarding certain stages of the VPg uridylylation process.

The initiation of picornavirus replication is featured by the uridylylation of viral protein genome-linked (VPg). In this process, viral RNA-dependent RNA polymerase (RdRp) catalyzes two uridine monophosphate (UMP) molecules to the hydroxyl group of the third tyrosine residue of VPg. Subsequently, the uridylylated VPg (VPg-pUpU) functions as the protein primer to initiate the replication of the viral genome. Although a large body of functional and structural works has been performed to define individual snapshots for particular stages of the VPg uridylylation process, the formation, dynamics and mechanism of the whole VPg uridylylation complex still requires further elucidation. We would like to provide an overview of the current knowledge of the picornaviral VPg uridylylation complex in this paper.