While the fundamental goals of translation initiation are the same for all cells, it is the most phylogenetically diverse step within translation. Until recently, there has been no evidence of a molecular mechanism that can initiate translation in both prokaryotes and eukaryotes. Colussi et al. (2015) reported that the eukaryotic PSIV IGR IRES can initiate prokaryotic translation and effectively circumvent domain-specific divergences. This novel discovery led us to investigate whether this IRES is unique in its ability to initiate prokaryotic translation and attempt to elucidate any distinguishing characteristics that allow for its mechanism of action to occur. Our results indicate that this IRES is unique in its ability to initiate prokaryotic translation. It also appears that the structural integrity of this IRES is less critical in prokaryotes than eukaryotes, and complementary interactions between Domain III and the 16S rRNA may contribute to this IRES' mechanism of action.