期刊
NUCLEIC ACIDS RESEARCH
卷 49, 期 12, 页码 6722-6738出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkab465
关键词
-
资金
- European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme [769080]
- Medical Research Council [MR/K024213/1]
- Lister Research Prize Fellowship
- Wellcome Trust [097462/Z/11/Z]
- Royal Society Wolfson Research Merit Award [WRM\R1\180008]
- Wellcome Trust GRE Centre Award [097945/Z/11/Z]
- ERC
- European Research Council (ERC) [769080] Funding Source: European Research Council (ERC)
- MRC [MR/K024213/1] Funding Source: UKRI
- Wellcome Trust [097945/Z/11/Z, 097462/Z/11/Z] Funding Source: Wellcome Trust
The study reveals that RNMT plays a crucial role in T cell activation by regulating ribosome biogenesis, which is essential for cellular metabolic reprogramming, proliferation, and differentiation. RNMT selectively regulates the expression of mRNAs targeted by the (m7)G-cap binding protein LARP1, impacting ribosome synthesis and translation rates.
The (m7)G cap is ubiquitous on RNAPII-transcribed RNA and has fundamental roles in eukaryotic gene expression, however its in vivo role in mammals has remained unknown. Here, we identified the (m7)G cap methyltransferase, RNMT, as a key mediator of T cell activation, which specifically regulates ribosome production. During T cell activation, induction of mRNA expression and ribosome biogenesis drives metabolic reprogramming, rapid proliferation and differentiation generating effector populations. We report that RNMT is induced by T cell receptor (TCR) stimulation and co-ordinates the mRNA, snoRNA and rRNA production required for ribosome biogenesis. Using transcriptomic and proteomic analyses, we demonstrate that RNMT selectively regulates the expression of terminal polypyrimidine tract (TOP) mRNAs, targets of the (m7)G-cap binding protein LARP1. The expression of LARP1 targets and snoRNAs involved in ribosome biogenesis is selectively compromised in Rnmt cKO CD4 T cells resulting in decreased ribosome synthesis, reduced translation rates and proliferation failure. By enhancing ribosome abundance, upregulation of RNMT coordinates mRNA capping and processing with increased translational capacity during T cell activation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据