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VPg
VPg (viral protein genome-linked) is a protein that is covalently attached to the 5′ end of positive strand viral RNA and acts as a primer during RNA synthesis in a variety of virus families including Picornaviridae and Caliciviridae. The primer activity of VPg occurs when the protein becomes uridylylated, providing a free hydroxyl that can be extended by the virally encoded RNA-dependent RNA polymerase. Aside from functioning as a primer, VPg also has a role in translation initiation by acting like a 5' mRNA cap. VPg was first described in initial investigations of poliovirus RNA as a protein covalently attached to the 5' end of the genome.〔Flanegan JB, Petterson RF, Ambros V, Hewlett MJ, Baltimore D. Covalent linkage of a protein to a defined nucleotide sequence at the 5′-terminus of virion and replicative intermediate rnas of poliovirus. Proc Natl Acad Sci U SA. 1977;74:961–965.〕〔Lee YF, Nomoto A, Detjen BM, Wimmer E. The genome-linked protein of picornaviruses i. A protein covalently linked to poliovirus genome rna. Proc Natl Acad Sci U S A. 1977;74:59–63.〕 and later seen in caliciviruses.〔Schaffer FL, Ehresmann DW, Fretz MK, Soergel MI. A protein, vpg, covalently linked to 36s calicivirus rna. J Gen Virol. 1980;47(1):215–220.〕 ==Attachment during RNA synthesis== VPg must undergo post-translational uridylylation before it can act as a primer for replication. 3Dpol (the RdRp) is able to synthesize Vpg-pUpU-OH by using a polyA sequence within a stem-loop structure (cis-acting replication element) of 2C-ATPase as a template.〔Goodfellow I, Chaudhry Y, Richardson A, Meredith J, Almond J W, Barclay W, Evans D J. Identification of a cis-acting replication element within the poliovirus coding region. J Virol. 2000;74:4590–4600.〕〔Paul A V, Rieder E, Kim D W, van Boom J H, Wimmer E. Identification of an RNA hairpin in poliovirus RNA that serves as the primary template in the in vitro uridylylation of VPg. J Virol. 2000;74:10359–10370.〕〔Rieder E, Paul A V, Kim D W, van Boom J H, Wimmer E. Genetic and biochemical studies of poliovirus cis-acting replication element cre in relation to VPg uridylylation. J Virol. 2000;74:10371–10380.〕 Furthermore, a 5' terminal cloverleaf is required in cis to form the 3Dpol preinitiation RNA replication complex involved in uridylylating VPg.〔Lyons T, Murray KE, Roberts AW, Barton DJ. Poliovirus 5′-terminal cloverleaf RNA is required in cis for VPg uridylylation and the initiation of negative-strand RNA synthesis. J Virol. 2001;75(22):10696–708.〕 3CDpro (a protease) cleaves VPg from membrane-bound 3AB.
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