Mechanisms of internal initiation on eukaryotic and viral mRNAs: the role of RNA structure

A number of mRNAs, including those of picornaviruses, contain internal ribosome entry sites (IRESs) in their 5ʹ UTR that enable cap-independent initiation to occur. IRES elements are large, typically 450 nucleotides in length, and contain extensive secondary and tertiary structure established by RNA-RNA and RNA protein interactions, they interact with a variety of cellular proteins. The function of an IRES element is entirely dependent on the correct integrity of the IRES structure, capable of initiating translation with significantly less initiation factors than those required for eukaryotic mRNAs. This allows translation continues when cellular translational machinery is inhibited by viral proteases. Typically, the actual ribosome entry site is at an AUG triplet located at the 3ʹ end of the IRES. According to the structural and functional properties, the IRES elements of the Picornaviridae are classified into four groups. Interestingly, the newly discovered group IV is fundamentally different from others and depicts properties highly reminiscent of the Flaviviridae IRES elements. 1. Translation initiation on eukaryotic mRNAs Translation of eukaryotic mRNAs is divided into