Dynamics in protein translation sustaining T cell preparedness

T Wolf, W Jin, G Zoppi, IA Vogel, M Akhmedov… - Nature …, 2020 - nature.com
T Wolf, W Jin, G Zoppi, IA Vogel, M Akhmedov, CKE Bleck, T Beltraminelli, JC Rieckmann…
Nature immunology, 2020nature.com
In response to pathogenic threats, naive T cells rapidly transition from a quiescent to an
activated state, yet the underlying mechanisms are incompletely understood. Using a pulsed
SILAC approach, we investigated the dynamics of mRNA translation kinetics and protein
turnover in human naive and activated T cells. Our datasets uncovered that transcription
factors maintaining T cell quiescence had constitutively high turnover, which facilitated their
depletion following activation. Furthermore, naive T cells maintained a surprisingly large …
Abstract
In response to pathogenic threats, naive T cells rapidly transition from a quiescent to an activated state, yet the underlying mechanisms are incompletely understood. Using a pulsed SILAC approach, we investigated the dynamics of mRNA translation kinetics and protein turnover in human naive and activated T cells. Our datasets uncovered that transcription factors maintaining T cell quiescence had constitutively high turnover, which facilitated their depletion following activation. Furthermore, naive T cells maintained a surprisingly large number of idling ribosomes as well as 242 repressed mRNA species and a reservoir of glycolytic enzymes. These components were rapidly engaged following stimulation, promoting an immediate translational and glycolytic switch to ramp up the T cell activation program. Our data elucidate new insights into how T cells maintain a prepared state to mount a rapid immune response, and provide a resource of protein turnover, absolute translation kinetics and protein synthesis rates in T cells (https://www.immunomics.ch).
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