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A 5′–3′ end interaction leading to stimulation of translation has been described for many cellular and viral mRNAs. Enhancement of viral translational efficiency mediated by 5′ and 3′ untranslated regions (UTRs) has been shown to occur via RNA–RNA interactions or novel RNA–protein interactions. Mammalian RNA viruses make use of end-to-end communication in conjunction with both viral and cellular factors to regulate multiple processes including translation initiation and the switch between translation and RNA synthesis during the viral lifecycle.