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PXD042145

PXD042145 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSaccharomyces cerevisiae translational fidelity
DescriptionAminoacyl-tRNA synthetases (aaRSs) are essential enzymes that ligate amino acids to tRNAs, and often require editing to ensure accurate protein synthesis. Recessive mutations in aaRSs cause various neurological disorders in humans, yet the underlying mechanism remains poorly understood. Pathogenic aaRS mutations frequently cause protein destabilization and aminoacylation deficiency. In this study, we report that combined aminoacylation and editing defects cause severe proteotoxicity. We show that a C268A mutation in yeast threonyl-tRNA synthetase (ThrRS) abolishes editing and causes heat sensitivity. Surprisingly, directed-evolution of the C268A mutant result in intragenic mutations that restore heat resistance but not editing. C268A destabilizes ThrRS and decreases overall Thr-tRNAThr synthesis, and the suppressor mutations in the evolved strains improve aminoacylation. We further show that deficiency in ThrRS aminoacylation or editing alone is not sufficient to cause heat sensitivity, and that C268A impairs ribosome-associated quality control. Our results suggest that aminoacylation deficiency predisposes cells to proteotoxic stress.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:26:47.732.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJiqiang Ling
SpeciesList scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-05-11 06:23:17ID requested
12024-01-26 08:33:49announced
22024-10-22 06:26:51announced2024-10-22: Updated project metadata.
Publication List
Zhang H, Murphy P, Yu J, Lee S, Tsai FTF, van Hoof A, Ling J, Coordination between aminoacylation and editing to protect against proteotoxicity. Nucleic Acids Res, 51(19):10606-10618(2023) [pubmed]
10.1093/nar/gkad778;
Keyword List
submitter keyword: mistranslation,Aminoacyl-tRNA synthetase, protein synthesis
Contact List
Jiqiang Ling
contact affiliationUniversity of Maryland, College Park
contact emailjling12@umd.edu
lab head
Jiqiang Ling
contact affiliationUniversity of Maryland
contact emailjling12@umd.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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