Calicivirus translation initiation requires an interaction between VPg and eIF4E

Goodfellow, Ian; Chaudhry, Yasmin; Gioldasi, Ioanna.; Gerondopoulos, Andreas; Natoni, Alessandro; Labrie, Louisette; Laliberté, Jean‐François; Roberts, Lisa O.

doi:10.1038/sj.embor.7400510

Cited by 191 publications

(217 citation statements)

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“…4 porcine enteric calicivirus, and MNV have been used as model systems to study calicivirus biology. We and others have previously reported that caliciviruses use a novel protein-directed translation initiation mechanism that involves the binding of translation initiation factors to the VPg protein that is covalently linked to the 5Ј end of the viral RNA (18,19). This mechanism has not been demonstrated in any other animal RNA virus but shares some similarity with a mechanism proposed for members of the plant potyvirus family (20 -23).…”

mentioning

confidence: 81%

“…MNV-1, strain CW.1, was the generous gift of Herbert Virgin (Washington University, St. Louis, MO) and was propagated in the murine macrophage cell line RAW 264.7 as described (15). Antisera to LDV VPg was generated by immunization of New Zealand White rabbits with recombinant VPg, purified as previously described (19). Antiserum to eIF4G was the kind gift of Simon Morley (University of Sussex).…”

Section: Methodsmentioning

confidence: 99%

“…This mechanism has not been demonstrated in any other animal RNA virus but shares some similarity with a mechanism proposed for members of the plant potyvirus family (20 -23). In our previous studies, we demonstrated that the VPg proteins of both FCV and Lordsdale virus (LDV), a human norovirus, interact directly with the eIF4E component of the eIF4F complex (19). Translation of FCV VPg-linked mRNA was blocked by the eIF4E inhibitor protein, 4E-BP1, confirming a functional role for eIF4E and suggesting that the eIF4E-4G interaction is essential for FCV translation.…”

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confidence: 91%

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Caliciviruses Differ in Their Functional Requirements for eIF4F Components

Chaudhry

Nayak

Bordeleau

et al. 2006

Journal of Biological Chemistry

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Two classes of viruses, namely members of the Potyviridae and Caliciviridae, use a novel mechanism for the initiation of protein synthesis that involves the interaction of translation initiation factors with a viral protein covalently linked to the viral RNA, known as VPg. The calicivirus VPg proteins can interact directly with the initiation factors eIF4E and eIF3. Translation initiation on feline calicivirus (FCV) RNA requires eIF4E because it is inhibited by recombinant 4E-BP1. However, to date, there have been no functional studies carried out with respect to norovirus translation initiation, because of a lack of a suitable source of VPg-linked viral RNA. We have now used the recently identified murine norovirus (MNV) as a model system for norovirus translation and have extended our previous studies with FCV RNA to examine the role of the other eIF4F components in translation initiation. We now demonstrate that, as with FCV, MNV VPg interacts directly with eIF4E, although, unlike FCV RNA, translation of MNV RNA is not sensitive to 4E-BP1, eIF4E depletion, or foot-and-mouth disease virus Lb protease-mediated cleavage of eIF4G. We also demonstrate that both FCV and MNV RNA translation require the RNA helicase component of the eIF4F complex, namely eIF4A, because translation was sensitive (albeit to different degrees) to a dominant negative form and to a small molecule inhibitor of eIF4A (hippuristanol). These results suggest that calicivirus RNAs differ with respect to their requirements for the components of the eIF4F translation initiation complex.

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confidence: 81%

Section: Methodsmentioning

confidence: 99%

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confidence: 91%

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Caliciviruses Differ in Their Functional Requirements for eIF4F Components

Chaudhry

Nayak

Bordeleau

et al. 2006

Journal of Biological Chemistry

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129

199

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“…The VPg proteins of plant potyviruses and human caliciviruses are covalently linked to the 5Ј-end of the viral genome but also act as eIF4E-binding proteins (26,27). This apparently pro- Represses translation of mRNAs that bind FMRP LLLDKRKRSEC (22) a These were determined from sequence alignments.…”

Section: Binding Partners For Eif4ementioning

confidence: 99%

eIF4E: New Family Members, New Binding Partners, New Roles

Rhoads

2009

Journal of Biological Chemistry

145

169

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Eukaryotic initiation factor 4E (eIF4E) has long been known as the cap-binding protein that participates in recruitment of mRNA to the ribosome. A number of recent advances have not only increased our understanding of how eIF4E acts in translation but also uncovered non-translational roles. New structures have been determined for eIF4E in complex with various ligands and for other cap-binding proteins. We have also learned that most eukaryotic organisms express multiple eIF4E family members, some involved in general translation but others having specialized functions, including repression of translation. A number of new eIF4E-binding proteins have been reported, some of which tether it to specific mRNAs.The 7-methylguanosine-containing "cap" plays an essential role at each stage of the mRNA "life cycle": transcription, splicing, nuclear export, translation, translational repression, and degradation. This is mediated by specific cap-binding proteins, of which at least 10 have been discovered so far (supplemental Table S1). The most widely studied and best understood of these cap-binding proteins is eIF4E.2 eIF4E was discovered as a protein that promotes translation initiation, and most of the work on its structure, function, and regulation has been performed with this role in mind. As a canonical initiation factor involved in recruitment of mRNA to the ribosome, eIF4E has the potential to influence expression of virtually every protein in the cell. It is against this backdrop of eIF4E serving as a translational enhancer that discoveries over the past decade have been so surprising, that eIF4E can also function as a translational repressor. Another unexpected result of recent research is that nearly all eukaryotes express multiple eIF4E family members and that they can have different functions in the cell. A third research trend has been the discovery of new eIF4E-binding partners, some of which tether eIF4E to specific mRNAs. This minireview touches on all of these new directions in eIF4E research. Role of eIF4E in TranslationRecruitment of mRNA to the 43 S initiation complex to form the 48 S initiation complex requires eIF3, the poly(A)-binding protein, and the eIF4 proteins (Fig. 1B) (1). The eIF4 factors consist of eIF4A, a 46-kDa RNA helicase; eIF4B, a 70-kDa RNA-binding and RNA-annealing protein; eIF4E, a 25-kDa cap-binding protein; eIF4H, a 25-kDa protein that acts with eIF4B to stimulate eIF4A helicase activity; and eIF4G, a 185-kDa protein that co-localizes all of the other proteins involved in mRNA recruitment on the 40 S subunit.3 At least four cis-acting elements affect the efficiency of mRNA translation: the cap, the poly(A) tail, sequence elements in the 5Ј-UTR, and sequence elements in the 3Ј-UTR. It is well established that eIF4E stimulates translation of capped mRNAs, but mRNAs differ in their dependence on eIF4E. For instance, mRNAs with extensive 5Ј-UTR secondary structure have a greater requirement for the eIF4A-based unwinding machinery recruited by eIF4E (Fig. 1B) (2).The tertiary structures ...

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“…The calici-and potyviruses encode a peptide, VPg, that attaches to the 5' end of the viral genome and operationally associates with eIF4E enabling translation initiation. [22][23][24] The orthomyxovirus, influenza, maintains translation when eIF4E is inhibited. 25 It remains to be seen whether eIF4G and eIF4A are required for translation in influenza-infected cells or whether the entire the cap-binding complex is circumvented.…”

Section: Bunyavirus N Protein Is a Translation Initiation Factormentioning

confidence: 99%