Nup100 regulates replicative life span by mediating the nuclear export of specific tRNAs.

Lord CL, Ospovat O, Wente SR
RNA. 2017 23 (3): 365-377

PMID: 27932586 · PMCID: PMC5311497 · DOI:10.1261/rna.057612.116

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) of We previously reported that deletion of the nonessential gene increases RLS, although the molecular basis for this effect was unknown. In this study, we find that nuclear tRNA accumulation contributes to increased longevity in Δ cells. Fluorescence in situ hybridization (FISH) experiments demonstrate that several specific tRNAs accumulate in the nuclei of Δ mutants. Protein levels of the transcription factor Gcn4 are increased when is deleted, and is required for the elevated life spans of Δ mutants, similar to other previously described tRNA export and ribosomal mutants. Northern blots indicate that tRNA splicing and aminoacylation are not significantly affected in Δ cells, suggesting that Nup100 is largely required for nuclear export of mature, processed tRNAs. Distinct tRNAs accumulate in the nuclei of Δ and Δ 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 the life span.

© 2017 Lord et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

MeSH Terms (16)

Active Transport, Cell Nucleus Basic-Leucine Zipper Transcription Factors Blotting, Northern Cell Division Cell Nucleus Culture Media Gene Expression Regulation, Fungal In Situ Hybridization, Fluorescence Karyopherins Nuclear Pore Nuclear Pore Complex Proteins RNA, Fungal RNA, Transfer Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Time Factors

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