Evolutionarily conserved RNAs in untranslated regions are key regulators of the viral life cycle. Exoribonuclease-resistant RNAs (xrRNAs) are particularly interesting examples of structurally conserved elements because they actively dysregulate the messenger RNA (mRNA) degradation machinery of host cells, thereby mediating viral pathogenicity. We review the principles of RNA structure conservation in viruses and discuss potential applications of xrRNAs in synthetic biology and future mRNA vaccines.