Structural RNA elements involved in internal initiation of translation

Introduction Initiation of protein translation on several viral genomes and a growing number of eukaryotic mRNAs has been shown to occur independently of a 5’ m7GpppX cap and to require a specialised RNA structure, an internal ribosome entry site (IRES). Cap-independent initiation of translation was first described for picornaviruses. The uncapped 5’ UTR of each picornaviral RNA genome contains an ordered structure of 400-450 nt that allows assembly of the translational machinery at a position close to, or directly at, the initiation codon. The picornavirus IRESs have been classified into 2 major types based on their structures. Entero/rhinoviruses have a type 1 IRES whereas aphtho-/cardioviruses contain a type 2 IRES. These IRES groups differ in host protein requirements, as well as the position of the initiation codon in relation to the entry site. IRES mediated translation has more recently been demonstrated for several other RNA viruses. These include members of the family Flaviviridae, the pestiviruses [classical swine fever virus (CSFV) and bovine viral diarrhoea virus (BVDV)] and hepaciviruses [hepatitis C virus (HCV)]. IRESs have also been found within the coding regions of some viral bicistronic mRNAs where they mediate translation of alternative open reading frames (e.g. retroviruses and cricket paralysis virus). Subsequently, the DNA virus associated with Kaposi’s sarcoma, human herpes virus 8 (HHV8), has been shown to translate the FLICE inhibitory protein, FLIP from an IRES which is located within the vcyclin coding region of a bicistronic mRNA and extends into the FLIP gene itself.