19 Initiation of Translation by Picornavirus RNAs

Abstract

About 15 years ago, soon after the initial development of methods to apply recombinant DNA and powerful sequencing technology to RNA molecules, the complete sequence of poliovirus RNA was determined (Kitamura et al. 1981; Racaniello and Baltimore 1981). It was immediately apparent that the primary structure of the 5′ end of the viral RNA was inconsistent with the cap-dependent scanning model for translation initiation that was so successfully being developed and presented for most cellular and viral messenger RNAs (Kozak 1978Kozak 1989). There was a striking absence of an m 7 G cap on the 5′ terminus of poliovirus RNA, and the initiating AUG codon was located at a position 743 nucleotides downstream from the 5′ end. The resulting long 5′-untranslated region (5′ UTR) contained numerous unused AUG triplets as well as a complex predicted secondary structure that would present significant obstacles to a scanning ribosome. Evidence for an alternate ribosome-binding and translation initiation mechanism accumulated slowly, until poliovirus and another related viral RNA, encephalomyocarditis virus (EMCV) RNA, became the first demonstrated examples of cap-independent internal translation initiation (Jang et al. 1988; Pelletier and Sonenberg 1988). The sequences and structures within the viral 5′ UTR required for translation initiation are known as the internal ribosome entry site (IRES). The rationale for evolving a unique structure and mechanism of ribosome binding in the case of these rapidly growing, lytic viruses might appear to be to enable the viruses to interfere with cellular translation, thereby eliminating competition for essential cellular components, and to more...