Ribosome profiling unveils translational regulation of metabolic enzymes in primary CD4+ Th1 cells

Abstract

The transition from a naïve to an effector T cell is an essential event that requires metabolic reprogramming. We have recently demonstrated that the rapid metabolic changes that occur following stimulation of naïve T cells require the translation of preexisting mRNAs. Here, we provide evidence that translation regulates the metabolic asset of effector T cells. By performing ribosome profiling in human CD4⁺ Th1 cells, we show that the metabolism of glucose, fatty acids and pentose phosphates is regulated at the translational level. In Th1 cells, each pathway has at least one enzyme regulated at the translational level and selected enzymes have high translational efficiencies. mRNA expression does not predict protein expression. For instance, PKM2 mRNA is equally present in naïve T and Th1 cells, but the protein is abundant only in Th1. 5'-untranslated regions (UTRs) may partly account for this regulation. Overall we suggest that immunometabolism is controlled by translation.

Keywords: Metabolism; PKM2; Ribosome profiling; Th1 cells; Translation; eIF4E; eIF6; mTORC1.