PXD034180

PXD034180 is an original dataset announced via ProteomeXchange.

Title	Perserverence of protein homeostasis despite mistranslation of glycine codons with alanine
Description	By physically linking amino acids to their codon assignments, transfer RNAs (tRNAs) are essential for protein synthesis and translation fidelity. Some natural human tRNA variants cause amino acid mis-incorporation at a codon or set of codons. Recent work showed a naturally occurring tRNASer variant decodes phenylalanine codons with serine and inhibits protein synthesis. We hypothesized that human tRNA variants that mis-read glycine (Gly) codons with alanine (Ala) will disrupt protein homeostasis. The A3G mutation occurs naturally in tRNAGly variants (tRNAGlyCCC, tRNAGlyGCC) and creates an alanyl-tRNA synthetase (AlaRS) identity element (G3:U70). Because AlaRS does not recognize the anticodon, the human tRNAAlaAGC G35C (tRNAAlaACC) variant may function similarly to mis-incorporate Ala at Gly codons. The tRNAGly and tRNAAla variants had no effect on protein synthesis in mammalian cells under normal growth conditions, however, tRNAGlyGCC A3G depressed protein synthesis in the context of proteasome inhibition. Mass spectrometry confirmed Ala mistranslation at several Gly codons caused by the tRNAGlyGCC A3G and tRNAAlaAGC G35C mutants, and in some cases, we observed multiple mistranslation events in the same peptide. The data reveal mistranslation of Ala at Gly codons and defects in protein homeostasis generated by natural human tRNA variants that are tolerated under normal conditions.
HostingRepository	PRIDE
AnnounceDate	2024-05-21
AnnouncementXML	Submission_2024-05-21_09:17:02.836.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD034180
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Farah Hasan
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monomethylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-29 13:44:35	ID requested
⏵ 1	2024-05-21 09:17:03	announced

10.6019/PXD034180;

10.1098/rstb.2022.0029;

Hasan F, Lant JT, O'Donoghue P, Perseverance of protein homeostasis despite mistranslation of glycine codons with alanine. Philos Trans R Soc Lond B Biol Sci, 378(1871):20220029(2023) [pubmed]

submitter keyword: tRNA, amino acid misincorporation, mistranslation

Patrick O'Donoghue
contact affiliation	Department of Biochemistry, Department of Chemistry, The University of Western Ontario, London, Ontario, Canada
contact email	podonog@uwo.ca
lab head
Farah Hasan
contact affiliation	University of Western Ontario
contact email	fhasan8@uwo.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034180
     1. Label: PRIDE project
     2. Name: Perserverence of protein homeostasis despite mistranslation of glycine codons with alanine