1887

Abstract

Translational readthrough-promoting drugs enhance the incorporation of amino acids at stop codons and can thus bypass premature termination during protein synthesis. The polymerase (Pol) proteins of Moloney murine leukemia virus (MoMLV) are synthesized as a large Gag–Pol fusion protein, formed by the readthrough of a stop codon at the end of the ORF. The downstream ORF lacks its own start codon, and Pol protein synthesis is wholly dependent on translation of the upstream gene and the readthrough event for expression. Here, we explored the effects of readthrough-promoting drugs – aminoglycoside antibiotics and the small molecule ataluren – on the efficiency of readthrough of the stop codon in the context of the MoMLV genome. We showed that these compounds increased readthrough of the stop codon at the MoMLV junction above the already high basal level and that the resulting elevated readthrough had deleterious effects on virus replication. We also showed that readthrough efficiency could be driven to even higher levels , and that the combination of the small molecules and the RNA structure at the MoMLV stop codon could achieve extremely high readthrough efficiencies.

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2015-11-01
2024-03-29
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