Modeling Three-Dimensional Structural Motifs of Viral IRES

RNA virus genomes are reservoirs of a wide diversity of RNA structural elements. In particular, specific regions of the viral genome have evolved to adopt specialized three-dimensional (3D) structures, which can act in concert with host factors and/or viral proteins to recruit the translation machinery on viral RNA using a mechanism that is independent on the 5' end. This strategy relies on cis-acting RNA sequences designated as internal ribosome entry site (IRES) elements. IRES elements that are found in the genome of different groups of RNA viruses perform the same function despite differing in primary sequence and secondary RNA structure and host factor requirement to recruit the translation machinery internally. Evolutionarily conserved motifs tend to preserve sequences in each group of RNA viruses impacting on RNA structure and RNA-protein interactions important for IRES function. However, due to the lack of sequence homology among genetically distant IRES elements, accurate modeling of 3D IRES structure is currently a challenging task. In addition, as a universal RNA motif unique to IRES elements has not been found, a better understanding of viral IRES structural motifs could greatly assist in the detection of IRES-like motifs hidden in genome sequences. The focus of this review is to describe recent advances in modeling viral IRES tertiary structural motifs and also novel approaches to detect sequences potentially folding as IRES-like motifs.