Transcriptome and proteome response is uncoupled under glutamine limitation
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. Overall design: MCF10A human breast epithelial cells were cultured in glutamine-free DMEM/F12 supplemented with four different concentrations of glutamine (0.04, 0.12, 0.20, and 0.28 mM) as well as normal glutamine concentration in DMEM/F12 (2.5 mM). Each glutamine condition included three biological replicates.