PXD033426-1

PXD033426 is an original dataset announced via ProteomeXchange.

Title	Amino acid substituents as a response to amino acid restriction
Description	Correct charging of tRNAs with their corresponding amino acid is crucial for accurate translation of the genetic code into proteins. However, a growing body of evidence shows that unicellular organisms (bacteria and yeast) can sacrifice translational fidelity to preserve protein synthesis under deprivation of specific essential amino acids.1 Several weeks ago, Pataskar and colleagues described the first instance of codon reassignments caused by amino acid restriction in mammalian cells. Specifically, when human cancer cells were deprived of tryptophan (W), tRNATrp was misacylated with the structurally similar amino acid phenylalanine (F) by tryptophanyl-tRNA synthetase (WARS1), resulting in W>F substitutions in synthesized proteins.2 The authors show that W>F substitutions do preserve translation, but generally result in dysfunctional proteins and that presentation of W>F peptides stimulates T cell-mediated killing. Together this would impair survival of cancer cells that incorporate W>F substitutions in their proteome.2 In the context of growing interest in amino acid depletion diets and related disorders,2 we wondered whether amino acid substitutions are restricted to pathological states like cancer or may represent a more generalized mechanism to maintain translation despite unfavorable circumstances. It is known that ARSs can misactivate tRNAs with structurally similar amino acids3, but editing activity ensures extreme specificity under physiological conditions.4,5 Given the structural similarities between isoleucine and valine, we speculated that isoleucyl-tRNA synthetase (IARS1) would misacylate tRNAIle with valine under isoleucine restriction, leading to I>V substitutions in the proteome. Not only did these substitutions occur in healthy primary human cells, but they also preserved translation and promoted cell viability upon nutritional stress.
HostingRepository	PRIDE
AnnounceDate	2024-11-26
AnnouncementXML	Submission_2024-11-26_09:13:00.207.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Harmjan Vos
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-24 12:42:52	ID requested
⏵ 1	2024-11-26 09:13:00	announced

10.1093/NAR/GKAE1184;

submitter keyword: isoleucyl-tRNA synthetase,translational fidelity, IARS1, Substitution

Sabine A Fuchs
contact affiliation	Department of Metabolic Diseases, Wilhelmina Children’s Hospital, University Medical Center Utrecht, The Netherlands
contact email	s.fuchs@umcutrecht.nl
lab head
Harmjan Vos
contact affiliation	University Medical Center Utrecht Dept. Molecular Cancer Research
contact email	h.r.vos-3@umcutrecht.nl
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/2024/11/PXD033426

PRIDE project URI

• PRIDE
  1. PXD033426
     1. Label: PRIDE project
     2. Name: Amino acid substituents as a response to amino acid restriction