PXD064886

PXD064886 is an original dataset announced via ProteomeXchange.

Title	Mistranslation from endogenous tRNA variants in human pan-genome cell lines
Description	Errors in protein synthesis are thought to be rare, yet cells representing the diversity of life tolerate greatly elevated levels of error. One source of translation error in humans are anticodon mutations in transfer RNAs (tRNAs). We found a tRNA Ser AGA -2-3 variant (G35A) that occurs in 2% of the human population causes mis-incorporation of serine (Ser) at phenylalanine (Phe) codons. We developed a dual fluorescent reporter to quantify mis-incorporation levels in live cells, including β-lymphocyte lines from the 1000 genomes project with wild-type or mutant A35 alleles. The mutant cells showed reduced viability, and tRNA sequencing confirmed expression, hypo-modification of C32, and 5’- fragment generation of the mutant tRNA Ser AAA . Transfection with our fluorescent reporter and mass spectrometry confirmed Ser mis-incorporation. The data demonstrate that a natural human genome encoded tRNA mutant causes mistranslation. Our findings have important implications for translation fidelity in humans and the application of missense suppressor tRNAs in medicine.
HostingRepository	PRIDE
AnnounceDate	2026-02-23
AnnouncementXML	Submission_2026-02-23_08:35:50.375.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD064886
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Kyle Hoffman
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro; Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-11 09:53:37	ID requested
⏵ 1	2026-02-23 08:35:51	announced

10.6019/PXD064886;

submitter keyword: mistranslation, tRNA variants, translation error

Patrick O'Donoghue
contact affiliation	Department of Biochemistry, The University of Western Ontario, London, Ontario, Canada. 2 Bioinformatic Solutions Inc., Waterloo, Ontario, Canada. Department of Chemistry, The University of Western Ontario, London, Ontario, Canada.
contact email	podonog@uwo.ca
lab head
Kyle Hoffman
contact affiliation	Bioinformatics Solutions Inc.
contact email	khoffman@bioinfor.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD064886
     1. Label: PRIDE project
     2. Name: Mistranslation from endogenous tRNA variants in human pan-genome cell lines