A diverse group of viruses subvert the host translational machinery to promote viral genome translation. This process often involves altering canonical translation initiation factors to repress cellular protein synthesis while viral proteins are efficiently synthesized. The discovery of this strategy in picornaviruses, which is based on the use of internal ribosome entry site (IRES) elements, opened new avenues to study alternative translational control mechanisms evolved in different groups of RNA viruses. IRESs are cis-acting RNA sequences that adopt three-dimensional structures and recruit the translation machinery assisted by a subset of translation initiation factors and various RNA binding proteins. However, IRESs present in the genome of different RNA viruses perform the same function despite lacking conservation of primary sequence and secondary RNA structure, and differing in host factor requirement to recruit the translation machinery. Evolutionary conserved motifs tend to preserve sequences impacting on RNA structure and RNA-protein interactions important for IRES function. While some motifs are found in various picornavirus IRESs, others occur only in one type reflecting specialized factor requirements. This review is focused to describe recent advances on the principles and RNA structure features of picornavirus IRESs.
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