Translation of Encephalomyocarditis Virus RNA by Internal Ribosomal Entry

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Abstract
The positive-sense genomic RNAs of picornaviruses such as encephalomyocarditis virus (EMCV) have been widely used in studies of translation, resulting in significant advances, such as identification of mammalian Met-tRNA (Smith and Marcker 1970) and recognition of the initiation factor elF-4A (Wigle and Smith 1973; Blair etal. 1977). Analysis of picornavirus translation also revealed a fundamental difference between eukaryotic and prokaryotic mRNAs: initiation of translation is limited to a single 5’ proximal site (Jacobson and Baltimore 1968; Smith 1973), indicating that picornavirus genomes, and by implication all other eukaryotic mRNAs, are monocistronic. The EMCV genome does indeed contain a single large open reading frame, but further studies of picornavirus mRNAs revealed fundamental differences from standard eukaryotic mRNAs (such as the absence of a 5’ terminal capping group, and the presence of multiple AUG triplets and stable secondary structure upstream of the initiation codon) that proved incompatible with conventional models for the initiation of eukaryotic translation (Kozak 1991). The discovery that EMCV initiation results from entry of ribosomes into an internal segment of the 5’NCR (Jang et al. 1988) has revitalized studies of EMCV translation, and its internal ribosome entry site (IRES) is now used both as a model for analysis of this novel mechanism of eukaryotic gene expression, and as a genetic element, for example in expression vectors, to promote cap-independent internal initiation of translation.This review shall focus on EMCV translation, but will also consider translation of other cardioviruses and of the related aphtho-viruses and hepatoviruses.