IRES elements: Issues, controversies and evolutionary perspectives

Abstract

Internal ribosome entry site (IRES) elements are cis-acting RNA regions that have the capacity to recruit the translation machinery internally using a cap-independent mechanism. Distinct types of IRES elements present in the genome of various RNA viruses, and in a subset of cellular mRNAs, perform the same function despite lacking conservation of primary sequence and secondary RNA structure. Likewise, they also differ in the host factor requirement to recruit the ribosomal subunits. In spite of this diversity, evolutionarily conserved motifs preserve sequences impacting on RNA structure and RNA-protein interactions important for each type of IRES element. Notwithstanding the lack of a universal RNA motif unique to all IRES elements, understanding of the structural motifs important for IRES function could greatly improve the accuracy to predict IRES-like motifs hidden in genome sequences and, moreover, to decipher the evolutionary history of these regulatory elements. Here we discuss the evolutionary perspectives of IRES elements based on the diversity of cap-independent translation mechanisms and on the RNA structure features of currently known IRES elements contributing to their activit.