PXD042145 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Saccharomyces cerevisiae translational fidelity |
Description | Aminoacyl-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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:26:47.732.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Jiqiang Ling |
SpeciesList | scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-05-11 06:23:17 | ID requested | |
1 | 2024-01-26 08:33:49 | announced | |
⏵ 2 | 2024-10-22 06:26:51 | announced | 2024-10-22: 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 affiliation | University of Maryland, College Park |
contact email | jling12@umd.edu |
lab head | |
Jiqiang Ling |
contact affiliation | University of Maryland |
contact email | jling12@umd.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD042145
- Label: PRIDE project
- Name: Saccharomyces cerevisiae translational fidelity