title: Evidence against a direct role for the Upf proteins in frameshifting or nonsense codon readthrough.
abstract: The Upf proteins are essential for nonsense-mediated mRNA decay (NMD). They have also been implicated in the modulation of translational fidelity at viral frameshift signals and premature termination codons. How these factors function in both mRNA turnover and translational control remains unclear. In this study, mono- and bicistronic reporter systems were used in the yeast Saccharomyces cerevisae to differentiate between effects at the levels of mRNA turnover and those at the level of translation. We confirm that upfDelta mutants do not affect programmed frameshifting, and show that this is also true for mutant forms of eIF1/Sui1p. Further, bicistronic reporters did not detect defects in translational readthrough due to deletion of the UPF genes, suggesting that their function in termination is not as general a phenomenon as was previously believed. The demonstration that upf sui1 double mutants are synthetically lethal demonstrates an important functional interaction between the NMD and translation initiation pathway.
authors.affiliation: Department of Cell Biology and Molecular Genetics, 2135 Microbiology Building, University of Maryland, College Park, MD 20742, USA.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Harger
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Dinman
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D018389:Codon, Nonsense; D018388:Codon, Terminator; D004926:Escherichia coli / Q000235:genetics; D015977:Eukaryotic Initiation Factor-1 / Q000235:genetics / Q000378:metabolism; D016368:Frameshift Mutation; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005800:Genes, Fungal; D017930:Genes, Reporter; D007763:Lac Operon; D008156:Luciferases / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018389:Codon, Nonsense; D018388:Codon, Terminator; D015977:Eukaryotic Initiation Factor-1; D005656:Fungal Proteins; C092470:NMD2 protein, S cerevisiae; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C072076:SUI1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; C096360:UPF3 protein, S cerevisiae; D008156:Luciferases; C074151:NAM7 protein, S cerevisiae; D020365:RNA Helicases