title: Temperature-sensitive eIF5A mutant accumulates transcripts targeted to the nonsense-mediated decay pathway.
abstract: The highly conserved protein eIF5A found in Archaea and all eukaryotes uniquely contains the posttranslationally formed amino acid hypusine. Despite being essential the functions of this protein and its modification remain unclear. To gain more insight into these functions temperature-sensitive mutants of the human EIF5A1 were characterized in the yeast Saccharomyces cerevisiae. Expression of the point mutated form V81G in a DeltaeIF5A strain of yeast led to a strongly temperature-sensitive phenotype and to a significantly reduced protein level at restrictive temperature. The mutant showed accumulation of a subset of mRNAs that was also observed in nonsense-mediated decay (NMD)-deficient yeast strains. After short incubation at restrictive temperature the mutant exhibited increased half-lives of the intron containing CYH2 pre-mRNA and mature transcripts of NMD-dependent genes. Reduced telomere silencing and shortening was detected in the V81G mutant further supporting similarities to NMD-deficient strains. Our data suggest that eIF5A mediates important cellular processes like cell viability and senescence through its effects on the stability of certain mRNAs.
authors.affiliation: Department for Protein Analytics, Max Planck Institute for Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany. schrader@biochem.mpg.de
authors.forename: Rainer
authors.initials: R
authors.lastname: Schrader
authors.forename: Craig
authors.initials: C
authors.lastname: Young
authors.forename: Detlef
authors.initials: D
authors.lastname: Kozian
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hoffmann
authors.forename: Friedrich
authors.initials: F
authors.lastname: Lottspeich
mesh_terms: D006801:Humans; D009154:Mutation / Q000235:genetics*; D010448:Peptide Initiation Factors / Q000235:genetics* / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D013696:Temperature; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A