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VPg is a protein attached to the 5′ end of RNA during RNA synthesis in a wide variety of viruses including Picornaviridae such as foot-and-mouth disease virus and poliovirus. VPg stands for "viral protein genome-linked."

Attachment during RNA synthesis
3CDpro (a protease) cleaves VPg from membrane-bound 3AB. 3Dpol (picornavirus RNA polymerase) then synthesizes VPg-pUpU using the sequence AAACA from the CRE (cis-acting replication element) of the template strand. The 3Dpol-VPg-pUpU complex then moves to the 3′ poly(A) tail of the template strand and commences RNA synthesis using the pUpU sequence as a primer.