Internal ribosome entry sites (IRESs) are RNA elements that allow the translation initiation in a cap-independent manner by recruiting the ribosome to the mRNA for protein synthesis. Discovered in 1988 in the poliovirus RNA genome,34 IRES are characterized by several elements recognized by proteins involved in translation, such as IRES trans-acting factors (ITAFs), but also canonical initiation factors. IRESs are present in many viruses and in eukaryotic mRNAs involved in responses to stress conditions (hypoxia, heat shock, nutrient limitation) or in response to signals to survive, differentiate, proliferate, or undergo apoptosis.35
