Initiation of Translation of Picornavirus RNAs: Structure and Function of the Internal Ribosome Entry Site

Ellie Ehrenfeld; Natalya L. Teterina

doi:10.1128/9781555817916.ch14

Chapter 14 : Initiation of Translation of Picornavirus RNAs: Structure and Function of the Internal Ribosome Entry Site

Authors: Ellie Ehrenfeld¹, Natalya L. Teterina¹

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Affiliations: 1: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892

Content Type: Monograph

Publication Year: 2002

Category: Viruses and Viral Pathogenesis

Book DOI: 10.1128/9781555817916

Chapter DOI: 10.1128/9781555817916.ch14

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Abstract:

By the late 1970s, a skeleton of the translation mechanism utilized by the bulk of cellular mRNAs had been elucidated. More elegant proof of utilization of an internal ribosome entry site (IRES) on the viral RNA was provided by analysis of translation of bicistronic constructs engineered to encode two tandem protein sequences, separated by a viral 5' untranslated region (UTR). The RNA sequences that constitute an IRES extend through several hundred nucleotides and fold into complex, multidomain structures. To identify the nucleotide sequences and structures in the picornavirus 5' UTRs that contribute to IRES function, mutations were introduced into cDNAs to generate transcripts whose translation could be evaluated in vitro or in transfected cells. For the picornavirus RNAs, a relatively relaxed structure is predicted, with a long, central axis of shifting base pairs, with relatively stable stems, loops, helices, and branch points extending from the central backbone. The conserved motifs in the secondary structure elements that are essential for IRES activity are likely to facilitate RNA-RNA or RNA-protein interactions required to maintain a higher order structure needed for proper recognition of the IRES element by the translational machinery. The picornavirus IRES elements represent relatively large complex domains composed of multiple subdomains that require correct spatial orientation and interactions to carry out IRES function. Efficient translation of capped mRNAs in eukaryotic cells involves a synergistic dependence on the 5'-terminal cap structure and the 3'-terminal poly(A) tail.

Citation: Ehrenfeld E, Teterina N. 2002. Initiation of Translation of Picornavirus RNAs: Structure and Function of the Internal Ribosome Entry Site, p 159-169. In Semler B, Wimmer E (ed), Molecular Biology of Picornavirus. ASM Press, Washington, DC. doi: 10.1128/9781555817916.ch14

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Initiation of Translation of Picornavirus RNAs: Structure and Function of the Internal Ribosome Entry Site

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FIGURE 1

Schematic representation of bicistronic mRNAs and their translation products.

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10.1128/9781555817916/fig14-1.gif

FIGURE 1

Schematic representation of bicistronic mRNAs and their translation products.

/content/10.1128/9781555817916.chap14.fig14-2

FIGURE 2

Schematic representation of the predicted stem-loop structures in the (A) poliovirus, (B) EMCV, and (C) hepatitis A virus 5′ UTR of the viral RNAs.

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10.1128/9781555817916/fig14-2.gif

FIGURE 2

Schematic representation of the predicted stem-loop structures in the (A) poliovirus, (B) EMCV, and (C) hepatitis A virus 5′ UTR of the viral RNAs.

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