Viruses have evolved a number of translational control mechanisms to regulate the levels of expression of viral proteins on polycistronic mRNAs, including programmed ribosomal frameshifting and stop codon readthrough. More recently, another unusual mechanism has been described, that of termination-dependent re-initiation (also known as stop–start). Here, the AUG start codon of a 3′ ORF (open reading frame) is proximal to the termination codon of a uORF (upstream ORF), and expression of the two ORFs is coupled. For example, segment 7 mRNA of influenza B is bicistronic, and the stop codon of the M1 ORF and the start codon of the BM2 ORF overlap in the pentanucleotide UAAUG (stop codon of M1 is shown in boldface and start codon of BM2 is underlined). This short review aims to provide some insights into how this translational coupling process is regulated within different viral systems and to highlight some of the differences in the mechanism of re-initiation on prokaryotic, eukaryotic and viral mRNAs.

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