Protein synthesis is a three-stage process, consisting of initiation, elongation and termination. The final stage of gene expression involves numerous cellular proteins and RNAs. The initiation step is the primary focus for regulation. Translation initiation on the majority of cellular mRNAs is mediated by a mechanism involving recognition of the 5’ terminal cap-structure (m7GpppN). However, a different mechanism, termed internal initiation, was first shown to occur on certain uncapped viral mRNAs. An internal ribosome entry site (IRES) element present within the 5’ untranslated region (UTR) of the viral RNA directs initiation of protein synthesis at an internal position hundreds of nucleotides downstream from the 5’ terminus. IRES elements are highly structured and position the ribosome at, or just upstream of, the initiation codon. IRES elements have been found in certain cellular mRNAs; these generally encode proteins involved in apoptosis, cell cycle regulation or stress responses....More >< Less