title: Inactivation of NMD increases viability of sup45 nonsense mutants in Saccharomyces cerevisiae.
abstract: BACKGROUND
  The nonsense-mediated mRNA decay (NMD) pathway promotes the rapid degradation of mRNAs containing premature termination codons (PTCs). In yeast Saccharomyces cerevisiae, the activity of the NMD pathway depends on the recognition of the PTC by the translational machinery. Translation termination factors eRF1 (Sup45) and eRF3 (Sup35) participate not only in the last step of protein synthesis but also in mRNA degradation and translation initiation via interaction with such proteins as Pab1, Upf1, Upf2 and Upf3.
  
  
  RESULTS
  In this work we have used previously isolated sup45 mutants of S. cerevisiae to characterize degradation of aberrant mRNA in conditions when translation termination is impaired. We have sequenced his7-1, lys9-A21 and trp1-289 alleles which are frequently used for analysis of nonsense suppression. We have established that sup45 nonsense and missense mutations lead to accumulation of his7-1 mRNA and CYH2 pre-mRNA. Remarkably, deletion of the UPF1 gene suppresses some sup45 phenotypes. In particular, sup45-n upf1Delta double mutants were less temperature sensitive, and more resistant to paromomycin than sup45 single mutants. In addition, deletion of either UPF2 or UPF3 restored viability of sup45-n double mutants.
  
  
  CONCLUSIONS
  This is the first demonstration that sup45 mutations do not only change translation fidelity but also acts by causing a change in mRNA stability.
authors: Department of Genetics and Breeding, St Petersburg State University, Universitetskaya emb, 7/9, 199034, St Petersburg, Russia. shabels@mail.ru
authors: Svetlana
authors: S
authors: Chabelskaya
authors: Valentina
authors: V
authors: Gryzina
authors: Svetlana
authors: S
authors: Moskalenko
authors: Catherine
authors: C
authors: Le Goff
authors: Galina
authors: G
authors: Zhouravleva
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001483:Base Sequence; D018389:Codon, Nonsense / Q000235:genetics*; D015536:Down-Regulation; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D008969:Molecular Sequence Data; D010454:Peptide Termination Factors / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / 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; C092470:NMD2 protein, S cerevisiae; D010454:Peptide Termination Factors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C080775:SUP45 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; C096360:UPF3 protein, S cerevisiae; C074151:NAM7 protein, S cerevisiae; D020365:RNA Helicases
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