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Transcriptome and proteome response is uncoupled under glutamine limitation

ABSTRACT: Understanding the quantitative relationship between transcript and protein concentrations remains a key challenge in biology. Absolute measurements of both transcript and protein concentration is critical but has not been done in human cells yet. Additionally, within-gene correlations were determined across different tissues, allowing environmental and genetic variability. Here, we address these limitations by analyzing within-gene correlations across the human cell line MCF10A with decreasing concentrations of glutamine in tissue culture as the sole independent variable. We find that the transcriptome and proteome response is uncoupled: the transcriptome primarily reallocates its resources, while the proteome changes in total protein. Furthermore, high within-gene correlations are observed in specific functional groups. Furthermore, genes with high within-gene correlation share common gene features, with the 3’ UTR length shows the largest effect. These results will provide valuable insights that could improve the prediction of protein concentrations from transcripts in biomedical research and biotechnology.

ORGANISM(S): Homo sapiens

PROVIDER: GSE311524 | GEO | 2025/12/01

REPOSITORIES: GEO

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Project description:Plasmodium falciparum is the main causative agent of human malaria. During the intraerythrocytic development cycle, P. falciparum morphology changes dramatically from circulating young rings to sequestered mature trophozoites and schizonts. Sequestered forms contribute to the pathophysiology of severe malaria as the infected erythrocytes obstruct the microvascular flow in deep organs and induce local inflammation. However, the sequestration mechanism limits the access to the corresponding parasitic form in clinical samples from patients infected with P. falciparum. To complement this deficiency, we aimed to evaluate the relevance of mRNA study as a proxy of protein expression in sequestered parasites. To do so, we conducted a proteotranscriptomic analysis using five independent P. falciparum laboratory strains samples. RNA sequencing was performed on circulating ring stage parasites and LC-MS/MS on the corresponding sequestered mature forms. All analyzes were performed within the same development cycle for direct individual correlation. mRNA expression level was assessed at the circulating ring stage and the corresponding protein expression level was measured after 18h-24h of maturation to reach the mature trophozoite stage. Overall, our results showed a strong transcriptome/transcriptome and proteome/proteome correlation between samples. Moreover, strong correlations of mRNA and proteins expressions levels were found between ring stage transcriptomes and mature forms proteomes. However, twice more transcripts were identified at ring stage than proteins at mature trophozoite stage. A high level of transcript expression did not guarantee the detection of the corresponding protein. Finally, we pointed out discrepancies at the individual gene level. Taken together, our results show that transcripts and proteins expression are overall correlated. However, mRNA abundance is not a perfect proxy of protein expression at the individual level. Importantly, our study shows limitations of the “blind” use of RNA-seq and the importance of multi-omics approaches for P. falciparum blood stage study in clinical samples.

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Transcriptome and proteome response is uncoupled under glutamine limitation

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