Non-canonical Translation in Plant RNA Viruses

Abstract

Viral protein synthesis is completely dependent upon the host cell's translational machinery. Canonical translation of host mRNAs depends on structural elements such as the 5′ cap structure and/or the 3′ poly(A) tail of the mRNAs. Although many viral mRNAs are devoid of one or both of these structures, they can still translate efficiently using non-canonical mechanisms. Here, we review the tools utilized by positive-sense single-stranded (+ss) RNA plant viruses to initiate non-canonical translation, focusing on cis-acting sequences present in viral mRNAs. We highlight how these elements may interact with host translation factors and speculate on their contribution for achieving translational control. We also describe other translation strategies used by plant viruses to optimize the usage of the coding capacity of their very compact genomes, including leaky scanning initiation, ribosomal frameshifting and stop-codon readthrough. Finally, future research perspectives on the unusual translational strategies of +ssRNA viruses are discussed, including parallelisms between viral and host mRNAs mechanisms of translation, particularly for host mRNAs which are translated under stress conditions.

Differential use of 3’CITEs by the subgenomic RNA of Pea enation mosaic virus 2

“…Increased translation of p27 in the absence of AUG 26 would be expected if a ribosome leaky scanning mechanism is used for translation initiation at the closely spaced AUG 26 and AUG 27 (Firth and Brierley, 2012; Kozak, 1999; Miras et al , 2017; Thiebeauld et al , 2007). In leaky scanning, ribosomes occasionally bypass one or more initiation codons in a weak context and initiate translation downstream at an AUG in a stronger context.…”

“…Since egress of plant viruses requires living cells, they must translate their genomes in competition with continued translation of cellular mRNAs. Most viruses in these families have short 5′UTRs, which necessitates placement of ribosome-attracting elements in or near their 3′UTRs, with long-distance RNA:RNA interactions connecting these elements with the 5′ end of the genome (Miras et al , 2017; Simon and Miller, 2013). The 3′ location of translation elements would also enable tombusvirid and luteovirid gRNA and any 3′ co-terminal sgRNA to share the same 3′CITE-dependent translation mechanism.…”

“…However, eukaryotic canonical translation is nearly always monocistronic, with translation initiating near the 5′ end of the mRNA and then proceeding in a 5′ to 3′ direction until reaching a termination codon (Aitken and Lorsch, 2012; Jackson et al , 2010). To circumvent this limitation, polycistronic RNA viruses must use one or more non-canonical mechanism to synthesize their proteins, including internal ribosome entry, re-initiation, leaky scanning and translational recoding (Firth and Brierley, 2012; Miras et al , 2017). In addition, with the exception of viruses in the Potyviridae and Secoviridae that employ a polyprotein expression strategy for gRNA translation (Zaccomer et al , 1995), many RNA viruses produce at least one subgenomic RNA (sgRNA), which repositions downstream ORFs proximal to a 5′ end (Firth and Brierley, 2012; Miras et al , 2017).…”

“…To circumvent this limitation, polycistronic RNA viruses must use one or more non-canonical mechanism to synthesize their proteins, including internal ribosome entry, re-initiation, leaky scanning and translational recoding (Firth and Brierley, 2012; Miras et al , 2017). In addition, with the exception of viruses in the Potyviridae and Secoviridae that employ a polyprotein expression strategy for gRNA translation (Zaccomer et al , 1995), many RNA viruses produce at least one subgenomic RNA (sgRNA), which repositions downstream ORFs proximal to a 5′ end (Firth and Brierley, 2012; Miras et al , 2017). The majority of sgRNAs are 3′ co-terminal with the gRNA, although sgRNAs that are 5′ co-terminal are associated with some viruses (Gowda et al , 2003; Tatineni et al , 2009; Vives et al , 2002).…”

Structure of eIF4E in Complex with an eIF4G Peptide Supports a Universal Bipartite Binding Mode for Protein Translation

“…But nearly all of the eIF4E-dependent viruses belong to the family Potyviridae (Sanfaçon, 2015). In many of these cases, the resistance phenotype arises from disruption of the direct interaction between the potyviral genome-linked protein (VPg) and eIF4E (Léonard et al, 2004;Yeam et al, 2007;Charron et al, 2008;Miras et al, 2017a). Overall, two regions of eIF4E have been mapped to be involved in the interaction with VPg, one near the cap-binding pocket and another in the lateral surface of the protein.…”