Author summary The simplest eukaryotic protein synthesis mechanism to date is found within an internal ribosome entry site (IRES) from the dicistrovirus family. The IRES adopts an RNA structure that can directly bind to and manipulate the ribosome to initiate translation from a non-AUG codon. Using a bioinformatics pipeline, we identified >4700 viral genomes that have IRES-like structures, highlighting conserved elements and atypical genome arrangements that include an embedded IRES within viral open reading frames. Moreover, we identified IRES-like structure in other viral families suggesting widespread adoption of this viral translation strategy. This study highlights the diverse viral strategies utilizing RNA-driven mechanisms.

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