Competitive Translation Efficiency at the Picornavirus Type 1 Internal Ribosome Entry Site Facilitated by Viral<i>cis</i>and<i>trans</i>Factors

Dobrikova, Elena Y.; Grisham, Rachel N.; Kaiser, Constanze; Gromeier, Matthias

doi:10.1128/jvi.80.7.3310-3321.2006

Cited by 35 publications

(48 citation statements)

References 58 publications

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“…This confirms earlier findings which show that CBV3 IRES stimulation in infected cells occurs independent of eIF4GI cleavage (Roberts et al 1998;Dobrikova et al 2006). This may appear counterintuitive since Ct is a by-product of CBV3 infection.…”

Section: Discussionsupporting

confidence: 82%

“…We attribute this variance to inconsistent empirical systems, variable structure of reporter constructs, and inherent differences of in vivo vs. in vitro assays. Moreover, we previously reported that correctly configured enteroviral IRES reporters translate as efficiently as capped conventional mRNAs in vivo in the absence of viral alterations of the host cell translation machinery (Dobrikova et al 2006). Lastly, CBV3 IRES-mediated translation is responsive to PABP (Bradrick et al 2007), while translation at the c-myc IRES is not (Thoma et al 2004), indicating divergent initiation factor involvement.…”

Section: Discussionmentioning

confidence: 99%

“…A pcDNA5/TO/FRT/luc positive control vector was produced by subcloning an XhoI-NotI Renilla Luciferase (RLuc) fragment from pTNT (Dobrikova et al 2006). Stable, inducible cell lines were established using the Flp-In T-Rex System (Invitrogen) according to the manufacturer's instructions.…”

Section: Stable Cell Lines and Virusesmentioning

confidence: 99%

“…pcDNA5/TO/FRT/myc-eIF4GI-b and pcDNA5/TO/FRT/myc-Ct were constructed by subcloning NheI-NotI fragments of myctagged eIF4GI-b and Ct from corresponding pcDNA3.1 expression vectors (Dobrikova et al 2006). A pcDNA5/TO/FRT/luc positive control vector was produced by subcloning an XhoI-NotI Renilla Luciferase (RLuc) fragment from pTNT (Dobrikova et al 2006).…”

Section: Stable Cell Lines and Virusesmentioning

confidence: 99%

“…Finally, inducible eIF4GI-b or Ct cell lines were generated by transfecting host cell lines with corresponding vectors followed by blasticidin/ hygromycinB selection. Propagation and use of CBV3 and construction of CBV3 2A pro expression vectors are described elsewhere (Dobrikova et al 2006).…”

Section: Stable Cell Lines and Virusesmentioning

confidence: 99%

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Activation of cap-independent translation by variant eukaryotic initiation factor 4G in vivo

Kaiser¹,

Dobrikova²,

Bradrick³

et al. 2008

RNA

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Protein synthesis is tightly controlled by assembly of an intricate ribonucleoprotein complex at the m 7 GTP-cap on eukaryotic mRNAs. Ensuing linear scanning of the 59 untranslated region (UTR) is believed to transfer the preinitiation complex to the initiation codon. Eukaryotic mRNAs are characterized by significant 59 UTR heterogeneity, raising the possibility of differential control of translation initiation rate at individual mRNAs. Curiously, many mRNAs with unconventional, highly structured 59 UTRs encode proteins with central biological roles in growth control, metabolism, or stress response. The 59 UTRs of such mRNAs may influence protein synthesis rate in multiple ways, but most significantly they have been implicated in mediating alternative means of translation initiation. Cap-independent initiation bypasses strict control over the formation of initiation intermediates at the m 7 GTP cap. However, the molecular mechanisms that favor alternative means of ribosome recruitment are not understood. Here we provide evidence that eukaryotic initiation factor (eIF) 4G controls cap-independent translation initiation at the c-myc and vascular endothelial growth factor (VEGF) 59 UTRs in vivo. Cap-independent translation was investigated in tetracycline-inducible cell lines expressing either full-length eIF4G or a C-terminal fragment (Ct) lacking interaction with eIF4E and poly(A) binding protein. Expression of Ct, but not intact eIF4G, potently stimulated cap-independent initiation at the c-myc/VEGF 59 UTRs. In vitro RNA-binding assays suggest that stimulation of cap-independent translation initiation by Ct is due to direct association with the c-myc/VEGF 59 UTR, enabling 43S preinitiation complex recruitment. Our work demonstrates that variant translation initiation factors enable unconventional translation initiation at mRNA subsets with distinct structural features.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Stable Cell Lines and Virusesmentioning

confidence: 99%

Section: Stable Cell Lines and Virusesmentioning

confidence: 99%

Section: Stable Cell Lines and Virusesmentioning

confidence: 99%

See 3 more Smart Citations

Activation of cap-independent translation by variant eukaryotic initiation factor 4G in vivo

Kaiser¹,

Dobrikova²,

Bradrick³

et al. 2008

RNA

Self Cite

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Novel marker for recombination in the 3′-untranslated region of members of the species Human enterovirus A

Kok

2012

Arch Virol

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Human enterovirus A (HEV-A) is a species in the genus Enterovirus. Viruses belonging to this species are often responsible for hand, foot and mouth disease and associated acute neurological disease. Studies of the 3' untranslated region (UTR) of human enterovirus 71 (HEV71) revealed a possible role in virus replication. We compared the 3'-UTRs of all members of HEV-A and confirmed the presence of a secondary structure comprising three stem-loop domains (SLDs). SLD-Z is situated closest to the stop codon and has been shown previously to affect plaque morphology. The prototype strains of coxsackieviruses A4 (CVA4), CVA14, and CVA16 carried the longer group I SLD-Z, whilst other CVAs and HEV71 carried the shorter group II SLD-Z. We demonstrate the importance of SLD-Z as a marker for the emergence of newer strains of HEV71 and CVA16 through inter-typic recombination and propose that SLD-Z is a novel evolutionary marker for recombination in HEV-A.

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Role of RNA Structure Motifs in IRES-Dependent Translation Initiation of the Coxsackievirus B3: New Insights for Developing Live-Attenuated Strains for Vaccines and Gene Therapy

2013

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Internal ribosome entry site (IRES) elements are highly structured RNA sequences that function to recruit ribosomes for the initiation of translation. In contrast to the canonical cap-binding, the mechanism of IRES-mediated translation initiation is still poorly understood. Translation initiation of the coxsackievirus B3 (CVB3), a causative agent of viral myocarditis, has been shown to be mediated by a highly ordered structure of the 5' untranslated region (5'UTR), which harbors an IRES. Taking into account that efficient initiation of mRNA translation depends on temporally and spatially orchestrated sequence of RNA-protein and RNA-RNA interactions, and that, at present, little is known about these interactions, we aimed to describe recent advances in our understanding of molecular structures and biochemical functions of the translation initiation process. Thus, this review will explore the IRES elements as important RNA structures and the significance of these structures in providing an alternative mechanism of translation initiation of the CVB3 RNA. Since translation initiation is the first intracellular step during the CVB3 infection cycle, the IRES region provides an ideal target for antiviral therapies. Interestingly, the 5' and 3'UTRs represent promising candidates for the study of CVB3 cardiovirulence and provide new insights for developing live-attenuated vaccines.

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Competitive Translation Efficiency at the Picornavirus Type 1 Internal Ribosome Entry Site Facilitated by ViralcisandtransFactors

Cited by 35 publications

References 58 publications

Activation of cap-independent translation by variant eukaryotic initiation factor 4G in vivo

Activation of cap-independent translation by variant eukaryotic initiation factor 4G in vivo

Novel marker for recombination in the 3′-untranslated region of members of the species Human enterovirus A

Role of RNA Structure Motifs in IRES-Dependent Translation Initiation of the Coxsackievirus B3: New Insights for Developing Live-Attenuated Strains for Vaccines and Gene Therapy

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