Picornaviruses break the rules

Jackson, Richard J.

doi:10.1038/334292a0

Cited by 50 publications

(34 citation statements)

References 8 publications

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“…A cap-independent mechanism involving an internal ribosome entry site (IRES) has been identified in picornavirus messengers, which are uncapped and present a long 5Ј UTR (20,41). The presence of an IRES has also been reported for many viral (cardiovirus, rhinovirus, and aphthovirus) (21) and some cellular human (Bip, FGF-2, IGF-II, eIF4G, PDGF, and c-Myc) (2,13,33,37,50,51,53) messengers and in Drosophila antennapedia and ultrabithorax mRNAs (39,59).…”

mentioning

confidence: 97%

Two Independent Internal Ribosome Entry Sites Are Involved in Translation Initiation of Vascular Endothelial Growth Factor mRNA

Huez

Créancier

Audigier

et al. 1998

Molecular and Cellular Biology

278

265

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The mRNA of vascular endothelial growth factor (VEGF), the major angiogenic growth factor, contains an unusually long (1,038 nucleotides) and structured 5 untranslated region (UTR). According to the classical translation initiation model of ribosome scanning, such a 5 UTR is expected to be a strong translation inhibitor. In vitro and bicistronic strategies were used to show that the VEGF mRNA translation was cap independent and occurred by an internal ribosome entry process. For the first time, we demonstrate that two independent internal ribosome entry sites (IRESs) are present in this 5 UTR. IRES A is located within the 300 nucleotides upstream from the AUG start codon. RNA secondary structure prediction and site-directed mutagenesis allowed the identification of a 49-nucleotide structural domain (D4) essential to IRES A activity. UV cross-linking experiments revealed that IRES A activity was correlated with binding of a 100-kDa protein to the D4 domain. IRES B is located in the first half of the 5 UTR. An element between nucleotides 379 and 483 is required for its activity. Immunoprecipitation experiments demonstrated that a main IRES B-bound protein was the polypyrimidine tract binding protein (PTB), a well-known regulator of picornavirus IRESs. However, we showed that binding of the PTB on IRES B does not seem to be correlated with its activity. Evidence is provided of an original cumulative effect of two IRESs, probably controlled by different factors, to promote an efficient initiation of translation at the same AUG codon.

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mentioning

confidence: 97%

Two Independent Internal Ribosome Entry Sites Are Involved in Translation Initiation of Vascular Endothelial Growth Factor mRNA

Huez

Créancier

Audigier

et al. 1998

Molecular and Cellular Biology

278

265

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“…Recently, a role for these cellular polypeptides in poliovirus translation has been demonstrated (Blyn et al, 1997). The bulk of the remainder of the 5h UTR constitutes an internal ribosome entry site which allows cap-independent translation, allowing viral protein synthesis in infected cells where cellular translation is shut-off via the activity of the viral protease 2A (for review see Jackson, 1988 ;Jackson & Kaminski, 1995).…”

Section: Introductionmentioning

confidence: 99%

Binding of a cellular factor to the 3' untranslated region of the RNA genomes of entero- and rhinoviruses plays a role in virus replication.

Mellits

Meredith²,

Rohll³

et al. 1998

Journal of General Virology

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The presence of cellular factors that bind to the 3h untranslated region (UTR) of picornaviruses was investigated by electrophoretic mobility shift assays (EMSAs). A cellular factor(s) that binds specifically the 3h UTR of polio-, coxsackie-and rhinoviruses was detected. Furthermore, this factor(s) is distinct from those which bind to the 5h terminal 88 nt (the ' cloverleaf ') of poliovirus. Mutations within the 3h

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“…An alternate approach is expression of the multiple genes using a polycistronic expression vector that takes advantage of either IRES (Internal Ribosomal Entry Site) or 2A elements. Derived from a viral linker sequence, the IRES element allows for 5'-cap-independent ribosomal binding and translation initiation directly at the start codon of the downstream gene, thus enabling translation of multiple ORFs from a single mRNA (Jackson, 1988;Jang et al, 1988). Although known IRES sequences vary in length and sequence, certain secondary structures have been shown to be conserved and important for the function of the elements (Baird et al, 2006).…”

Section: Elements For Simultaneous Expression Of Multiple Genes In Eumentioning

confidence: 99%

Expression of Non-Native Genes in a Surrogate Host Organism

Close¹,

Xu²,

Smartt³

et al. 2012

Genetic Engineering - Basics, New Applications and Responsibilities

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Picornaviruses break the rules

Cited by 50 publications

References 8 publications

Two Independent Internal Ribosome Entry Sites Are Involved in Translation Initiation of Vascular Endothelial Growth Factor mRNA

Two Independent Internal Ribosome Entry Sites Are Involved in Translation Initiation of Vascular Endothelial Growth Factor mRNA

Binding of a cellular factor to the 3' untranslated region of the RNA genomes of entero- and rhinoviruses plays a role in virus replication.

Expression of Non-Native Genes in a Surrogate Host Organism

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