PXD038324-2

PXD038324 is an original dataset announced via ProteomeXchange.

Title	Transcriptomic, proteomic and functional consequences of codon usage bias in human cells
Description	Differences in codon frequency between genomes, genes, or positions along a gene, modulate transcription and translation efficiency, leading to phenotypic and functional differences. Integrative studies quantifying the phenotypic consequences of codon usage bias at different molecular and cellular levels in human cells are lacking. Here, we present a multiscale analysis of the effects of synonymous codon recoding during heterologous gene expression in human cells. Six synonymous versions of an antibiotic resistance gene were generated, fused to a fluorescent reporter, and independently expressed in HEK293 cells. Multiscale phenotype was analysed by means of: quantitative transcriptome and proteome assessment, as proxies for gene expression; cellular fluorescence, as a proxy for single-cell level expression; and real-time cell proliferation in absence or presence of antibiotic, as a proxy for the cell fitness. We show that differences in codon usage bias strongly impact the molecular and cellular phenotype: (i) they result in large differences in mRNA and in protein levels, as well in mRNA-to-protein ratio; (ii) they introduce unpredicted splicing events; (iii) they lead to reproducible phenotypic heterogeneity; and (iv) they lead to a trade-off between the benefit of antibiotic resistance and the burden of heterologous expression. In human cells in culture, codon usage bias modulates gene expression by modifying mRNA availability and suitability for translation, leading to differences in protein levels and eventually eliciting functional phenotypic changes.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:42:39.277.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Functional Proteomics Platform FPP
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-23 04:45:28	ID requested
1	2024-05-24 02:43:19	announced
⏵ 2	2024-10-22 06:42:40	announced	2024-10-22: Updated project metadata.

10.1002/pro.4576;

Picard MAL, Leblay F, Cassan C, Willemsen A, Daron J, Bauffe F, Decourcelle M, Demange A, Bravo IG, Transcriptomic, proteomic, and functional consequences of codon usage bias in human cells during heterologous gene expression. Protein Sci, 32(3):e4576(2023) [pubmed]

submitter keyword: culture, mass spectrometry,HEK-293

Ignacio G. Bravo
contact affiliation	Laboratory MIVEGEC (CNRS IRD University Montpellier), French National Center for Scientific Research (CNRS), Montpellier, France
contact email	ignacio.bravo@cnrs.fr
lab head
Functional Proteomics Platform FPP
contact affiliation	FPP CNRS
contact email	contact@fpp.cnrs.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD038324
     1. Label: PRIDE project
     2. Name: Transcriptomic, proteomic and functional consequences of codon usage bias in human cells