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蛋白质翻译中的动态变化维持 T 细胞的预备状态。

Dynamics in protein translation sustaining T cell preparedness.

机构信息

Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.

Institute of Microbiology, ETH Zürich, Zurich, Switzerland.

出版信息

Nat Immunol. 2020 Aug;21(8):927-937. doi: 10.1038/s41590-020-0714-5. Epub 2020 Jul 6.

DOI:10.1038/s41590-020-0714-5
PMID:32632289
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7610365/
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 ).

摘要

针对致病威胁,幼稚 T 细胞迅速从静止状态过渡到激活状态,但背后的机制尚不完全清楚。我们使用脉冲 SILAC 方法研究了人类幼稚和激活 T 细胞中 mRNA 翻译动力学和蛋白质周转率的动态变化。我们的数据集揭示了维持 T 细胞静止的转录因子具有固有较高的周转率,这使得它们在激活后能够迅速被消耗。此外,幼稚 T 细胞保持了大量空闲核糖体,以及 242 种受抑制的 mRNA 种类和糖酵解酶的储备。这些成分在受到刺激后迅速被募集,促进了立即的翻译和糖酵解转换,以加速 T 细胞激活程序。我们的数据阐明了 T 细胞如何保持准备状态以快速免疫反应的新见解,并提供了 T 细胞中蛋白质周转率、绝对翻译动力学和蛋白质合成率的资源(https://www.immunomics.ch)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57c0/7610365/bd55ec6165c5/EMS117975-f007.jpg
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