THE UPF3 PROTEIN IS A COMPONENT OF THE SURVEILLANCE COMPLEX THAT MONITORS BOTH TRANSLATION AND MESSENGER-RNA TURNOVER AND AFFECTS VIRAL PROPAGATION

The nonsense-mediated mRNA decay pathway functions to degrade aberrant mRNAs that contain premature translation termination codons. In Sacch aromyces cerevisiae, the Upf1, Upf2, and Upf3 proteins have been ident ified as trans-acting factors involved in this pathway. Recent results have demonstrated that the Upf proteins may also be involved in maint aining the fidelity of several aspects of the translation process. Cer tain mutations in the UPF1 gene have been shown to affect the efficien cy of translation termination at nonsense codons and/or the process of programmed -1 ribosomal frameshifting used by viruses to control thei r gene expression, Alteration of programmed frameshift efficiencies ca n affect virus assembly leading to reduced viral titers or elimination of the virus. Here we present evidence that the Upf3 protein also fun ctions to regulate programmed -1 frameshift efficiency. A upf3-Delta s train demonstrates increased sensitivity to the antibiotic paromomycin and increased programmed -1 ribosomal frameshift efficiency resulting in loss of the M-1 virus. Based on these observations, we hypothesize that the Upf proteins are part of a surveillance complex that functio ns to monitor translational fidelity and mRNA turnover.