3′ Cap-Independent Translation Enhancers of Plant Viruses

Abstract

In the absence of a 5′ cap, plant positive-strand RNA viruses have evolved a number of different elements in their 3′ untranslated region (UTR) to attract initiation factors and/or ribosomes to their templates. These 3′ cap-independent translational enhancers (3′ CITEs) take different forms, such as I-shaped, Y-shaped, T-shaped, or pseudoknotted structures, or radiate multiple helices from a central hub. Common features of most 3′ CITEs include the ability to bind a component of the translation initiation factor eIF4F complex and to engage in an RNA-RNA kissing-loop interaction with a hairpin loop located at the 5′ end of the RNA. The two T-shaped structures can bind to ribosomes and ribosomal subunits, with one structure also able to engage in a simultaneous long-distance RNA-RNA interaction. Several of these 3′ CITEs are interchangeable and there is evidence that natural recombination allows exchange of modular CITE units, which may overcome genetic resistance or extend the virus’s host range.

Pelarspovirus, a proposed new genus in the family Tombusviridae

“…The ORFs are flanked by untranslated regions (UTRs) of variable lengths. The 5 0 UTRs are short (14-43 nt) for PelRSV, PCRPV and ELV, or very short as found for PLPV and RrLDV, with just 5-6 nt ( Table 1) [9,27,35]. Nevertheless, experimental evidence for the functionality of the predicted structural motifs in the 3 0 UTR remains to be obtained.…”

“…Virions have either a bumpy or a smooth appearance in electron micrographs, depending on the presence or absence, respectively, of a C-terminal protruding domain in the corresponding CP [29,36]. General gene expression strategies include (i) translation of viral proteins facilitated by a 3 0 cap-independent translational enhancer (3 0 CITE) [29,35], (ii) synthesis of the RdRp as a C-terminal extension of the accessory replication protein by either ribosomal readthrough or frameshifting, (iii) leaky scanning of ribosomes on bicistronic or polycistronic viral mRNAs, which allows expression of downstream ORFs, and (iv) transcription of subgenomic (sg) RNAs during infections to template translation of genes located internally and 3 0 -proximally in the genomic (g) RNA. The demarcation criteria for genera in the family Tombusviridae are ''(A) structural criteria -spherical virions with either a smooth or granular appearance; (B) genomic criteriagenome organization, number of genome segments, size of genome; and (C) polymerase criteria -gene interrupted by a termination codon or a -1 ribosomal frameshifting element that is periodically read through'' [29].…”

Picornavirus IRES elements: RNA structure and host protein interactions

“…Different groups of viral RNAs that have evolved alternative manners to promote cap-independent translation initiation (reviewed in) (Simon and Miller, 2013), trigger translation initiation taking advantage of RNA structures that also generate functional bridges between the 5 and 3 UTRs of the viral RNA (see (Nicholson and White, 2014) for a comprehensive recent review). Together, these common features provide a mechanistic basis for cap-independent translation stimulation of viral RNAs resembling the synergistic stimulation of the cellular mRNA cap-dependent translation.…”

Recruitment of the 40S Ribosome Subunit to the 3′-Untranslated Region (UTR) of a Viral mRNA, via the eIF4 Complex, Facilitates Cap-independent Translation

“…Before RNA replication can commence, viral RNA must be translated in order to synthesize the viral replicase. To outcompete host mRNAs for the ribosomes and to evade host translational control mechanisms, positive strand RNA viruses have evolved a plethora of non-canonical translation initiation mechanisms (2,3); these include the powerful internal ribosome entry sites (IRESs) 2 of picornaviruses (4,5), hepatitis C virus (6,7), and dicistroviruses (8) as well as 3Ј-cap-independent translation elements (3Ј-CITEs) in plant viruses (9).…”

“…Unlike with IRESs, ribosome scanning from the 5Ј-end of the mRNA is required for translation of mRNAs relying on a 3Ј-CITE (9,(22)(23)(24). These include RNAs of plus-strand RNA viruses in the Tombusviridae family and the Luteovirus and Umbravirus genera, all of which lack both a 5Ј-cap and a 3Ј-poly(A) tail (23)(24)(25).…”