title: Nup100 regulatesSaccharomyces cerevisiaereplicative life span by mediating the nuclear export of specific tRNAs.
abstract: Nuclear pore complexes (NPCs), which are composed of nucleoporins (Nups) and regulate transport between the nucleus and cytoplasm, significantly impact the replicative life span (RLS) ofSaccharomyces cerevisiaeWe previously reported that deletion of the nonessential geneNUP100increases RLS, although the molecular basis for this effect was unknown. In this study, we find that nuclear tRNA accumulation contributes to increased longevity innup100Δ cells. Fluorescence in situ hybridization (FISH) experiments demonstrate that several specific tRNAs accumulate in the nuclei ofnup100Δ mutants. Protein levels of the transcription factor Gcn4 are increased whenNUP100is deleted, andGCN4is required for the elevated life spans ofnup100Δ mutants, similar to other previously described tRNA export and ribosomal mutants. Northern blots indicate that tRNA splicing and aminoacylation are not significantly affected innup100Δ cells, suggesting that Nup100 is largely required for nuclear export of mature, processed tRNAs. Distinct tRNAs accumulate in the nuclei ofnup100Δ andmsn5Δ mutants, while Los1-GFP nucleocytoplasmic shuttling is unaffected by Nup100. Thus, we conclude that Nup100 regulates tRNA export in a manner distinct from Los1 or Msn5. Together, these experiments reveal a novel Nup100 role in the tRNA life cycle that impacts theS. cerevisiaelife span.
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37240, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Lord
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37240, USA.
authors.forename: Ophir
authors.initials: O
authors.lastname: Ospovat
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37240, USA.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Wente
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015152:Blotting, Northern; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism*; D003470:Culture Media / Q000737:chemistry; D015966:Gene Expression Regulation, Fungal; D017404:In Situ Hybridization, Fluorescence; D028884:Karyopherins / Q000172:deficiency / Q000235:genetics; D022022:Nuclear Pore / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000172:deficiency / Q000235:genetics*; D012331:RNA, Fungal / Q000235:genetics* / Q000378:metabolism; D012343:RNA, Transfer / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D003470:Culture Media; C501391:GCN4 protein, S cerevisiae; D028884:Karyopherins; C408090:Los1 protein, S cerevisiae; C401306:MSN5 protein, S cerevisiae; C077731:NUP100 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D012331:RNA, Fungal; D029701:Saccharomyces cerevisiae Proteins; D012343:RNA, Transfer
keywords: aging; nuclear pore complex; tRNA