Internal Ribosome Entry Site Elements in Eukaryotic Genomes

Understanding of the full potential of the genome coding capacity demands a deep knowledge of the different pathways that control gene expression. Translation initiation in eukaryotic mRNAs is a highly regulated process that accounts for the last step of gene expression control. While most mRNAs initiate translation using the AUG triplet closest to the 5'end, a growing number of mRNAs appear to follow different rules, giving rise to proteins that differ in their amino terminus. Internal ribosome entry site (IRES) elements provide an alternative to initiate translation that allow the use of internal start codons, sometimes located several hundred of residues away from the 5'end of the mRNA, bypassing strong RNA structures. Therefore, they represent a strategy to increase genetic diversity without increasing genome length. The IRES sequences found in viral and cellular mRNAs do not show overall sequence similarity, albeit they perform a similar function. IRES elements in viral mRNAs constitute an efficient method to distinguish its own mRNA from that of the host, and thus facilitate its survival when cellular protein synthesis is impaired. Viral IRES exploit different strategies to recruit the translational machinery, including direct ribosome binding, eIF3 or eIF4G-mediated mechanism. Cellular IRES mediated-translation represents a regulatory mechanism that helps the cell to cope with transient stress. They may be grouped according to common tropism, stimulation by similar situations and expression of specific targets in differentiated cells. Protein mediated-ribosome binding is likely to enhance the efficiency of cellular IRES sequences under specific environments. This review is focused to discuss recent advances on functional IRES elements.