PXD034180 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-05-29 13:44:35 | ID requested | |
⏵ 1 | 2024-05-21 09:17:03 | announced | |
Publication List
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] |
Keyword List
submitter keyword: tRNA, amino acid misincorporation, mistranslation |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD034180
- Label: PRIDE project
- Name: Perserverence of protein homeostasis despite mistranslation of glycine codons with alanine