Limited but gene-class specific correlation of mRNA and protein expression in human CD8+ T cells

SUMMARY T cell differentiation and activation induces substantial alterations in gene expression. While RNA sequencing and single cell RNA sequencing analysis provided important insights in the gene expression dynamics of T cells, it is not well understood how the mRNA expression translates into the protein landscape. By combining paired RNA-sequencing and mass spectrometry data of primary human CD8 + T cells, we found that mRNA expression is a poor proxy for the overall protein output. Irrespective of the differentiation or activation status, the correlation coefficient of human CD8 + T cells reached a mere 0.41-0.43. Only gene classes that mediate conserved cellular processes such as protein translation or cellular metabolism showed a strong correlation of mRNA with protein expression. In contrast, the mRNA expression and protein output of transcription factors, cell surface molecules, and secreted proteins - including cytokines - only mildly correlated. Conversely, highly conserved genes correlated well with the protein output. This was also true for the presence of AU-rich elements in the 3’untranslated region, in particular for mRNAs that encode secreted proteins. In conclusion, the in-depth characterization of the transcriptome and proteome in human CD8 + T cells emphasizes the need of combined mRNA and protein analysis for our understanding of T cell biology and function.