Abstract
Nucleotidylylation is a post-transcriptional modification important for replication in the picornavirus supergroup of RNA viruses, including members of the Caliciviridae, Coronaviridae, Picornaviridae and Potyviridae virus families. This modification occurs when the RNA-dependent RNA polymerase (RdRp) attaches one or more nucleotides to a target protein through a nucleotidyl-transferase reaction. The most characterized nucleotidylylation target is VPg (viral protein genome-linked), a protein linked to the 5′ end of the genome in Caliciviridae, Picornaviridae and Potyviridae. The nucleotidylylation of VPg by RdRp is a critical step for the VPg protein to act as a primer for genome replication and, in Caliciviridae and Potyviridae, for the initiation of translation. In contrast, Coronaviridae do not express a VPg protein, but the nucleotidylylation of proteins involved in replication initiation is critical for genome replication. Furthermore, the RdRp proteins of the viruses that perform nucleotidylylation are themselves nucleotidylylated, and in the case of coronavirus, this has been shown to be essential for viral replication. This review focuses on nucleotidylylation within the picornavirus supergroup of viruses, including the proteins that are modified, what is known about the nucleotidylylation process and the roles that these modifications have in the viral life cycle.
Highlights
Positive-sense single-stranded (+ss) RNA viruses are an enormously diverse class of animal, plant and bacterial viruses
Analysis of positive-strand genomic RNA synthesis by a range of +ssRNA viruses shows that initiation can occur via a protein primer-dependent mechanism regulated by the nucleotidylylation of a VPg protein [4,5,6,7]
In murine norovirus (MNV) and human noroviruses (HuNV), nucleotidylylation is catalyzed by both forms of polymerase, the mature RNA-dependent RNA polymerase (RdRp) and the ORF1-derived precursor protein comprised of unprocessed protease-polymerase
Summary
Positive-sense single-stranded (+ss) RNA viruses are an enormously diverse class of animal, plant and bacterial viruses. Analysis of positive-strand genomic RNA synthesis by a range of +ssRNA viruses shows that initiation can occur via a protein primer-dependent mechanism regulated by the nucleotidylylation of a VPg protein (viral protein genome-linked) [4,5,6,7]. Regardless of the exact mechanism, nucleotidylylation is essential to the replication of a wide range of +ssRNA viruses, and this review will focus upon our understanding of the function and importance of nucleotidylylation during the life cycle of RNA viruses belonging primarily to the Caliciviridae, Coronaviridae, Picornaviridae and Potyviridae viral families (Figure 1)
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