The structure and function of a cis-acting element located upstream of the IRES that influences Coxsackievirus B3 RNA translation.

We have investigated the importance of a conserved hexa-nucleotide stretch in the apical loop within stem-loop C (SL C, nt 104-180), upstream of the ribosome landing site, on CVB3 IRES function. The deletion or substitution mutation at this apical loop resulted in significant decrease in IRES activity. Both the mutant IRES RNAs failed to interact with certain trans-acting factors. Furthermore, expression of CVB3 2A protease significantly enhanced IRES activity of the wild type, but the effect was not so pronounced on the mutant IRESs. It is possible that the mutant RNAs were unable to interact with some trans-acting factors critical for enhanced IRES function. Interestingly, the local structure of the IRES RNA was not significantly altered due to substitution mutation. Taken together, it appears that the SL C/c apical loop is critical for CVB3 IRES function.