PXD042145

PXD042145 is an original dataset announced via ProteomeXchange.

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

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.

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;

submitter keyword: mistranslation,Aminoacyl-tRNA synthetase, protein synthesis

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/01/PXD042145

PRIDE project URI

• PRIDE
  1. PXD042145
     1. Label: PRIDE project
     2. Name: Saccharomyces cerevisiae translational fidelity