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code availability nature portfolio nature immunology team privacy policy large-scale multi-omic analysis peer review references wolf lymphocyte populations21 editing advertising discussion subjects sharing multifactorial nature h-2db-restricted tcr specific social media quantitative metabolite information original author nat10-mediated n4-acetylcytidine modification {\rm{cd}}3^{+}{\rm{tcr}}\upbeta^{+}} nature 548 nature high-throughput ac4c rip–seq rna-seq service thermo fisher scientific reprints retroviral vectors pmxs-ires-gfp ethics committee national key research research hot spot research efforts directed acrip-seq service rights trna-m1a modification promotes acquity uplc-xevo tq high-throughput sequencing data whb scientific anti-cd3/cd28-stimulated cd3+ specific pathogen-free conditions anti-cd3/cd28 beads stimulation zhou-li cheng rna-seq datasets reveals uplc–ms/ms system phorbol 12-myristate 13-acetate/ionomycin jak–stat signaling pathways7 epitranscriptomic n4-acetylcytidine profiling rna-quick purification kit high-throughput sequencing reads cre/loxp recombination system clinical research

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• How, then, does NAT10 impact MYC protein levels?
• Prognostic and immunological role of mRNA ac4C regulator NAT10 in pan-cancer: new territory for cancer research?

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         headline:A critical role of N4-acetylation of cytidine in mRNA by NAT10 in T cell expansion and antiviral immunity
         description:Following activation, naive T cells exit quiescence and require global translation for rapid expansion, yet the underlying mechanisms remain unclear. Here, we show that during T cell activation, cells upregulate the expression of N-acetyltransferase 10 (NAT10), an enzyme responsible for N4-acetylcytidine (ac4C) modification of mRNAs. ac4C-modified Myc mRNAs show higher translation efficiency, enabling rapid synthesis of MYC protein and supporting robust T cell expansion. Conditional deletion of Nat10 in mouse T cells causes severe cell cycle arrest and limitation of cell expansion due to MYC deficiency, ultimately exacerbating infection in an acute lymphocytic choriomeningitis virus model. Additionally, T cells from older individuals with lower NAT10 levels show proliferative defects, which may partially account for impaired antiviral responses in older individuals. This study reveals a mechanism governing T cell expansion, signal-dependent mRNA degradation induction and the potential in vivo biological significance of ac4C modification in T cell-mediated immune responses. The authors show that NAT10 is upregulated with T cell antigen receptor signaling and that T cell-specific NAT10 deficiency results in diminished numbers of naive T cells, translating to an inability to mount a significant antiviral T cell response.
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      headline:A critical role of N4-acetylation of cytidine in mRNA by NAT10 in T cell expansion and antiviral immunity
      description:Following activation, naive T cells exit quiescence and require global translation for rapid expansion, yet the underlying mechanisms remain unclear. Here, we show that during T cell activation, cells upregulate the expression of N-acetyltransferase 10 (NAT10), an enzyme responsible for N4-acetylcytidine (ac4C) modification of mRNAs. ac4C-modified Myc mRNAs show higher translation efficiency, enabling rapid synthesis of MYC protein and supporting robust T cell expansion. Conditional deletion of Nat10 in mouse T cells causes severe cell cycle arrest and limitation of cell expansion due to MYC deficiency, ultimately exacerbating infection in an acute lymphocytic choriomeningitis virus model. Additionally, T cells from older individuals with lower NAT10 levels show proliferative defects, which may partially account for impaired antiviral responses in older individuals. This study reveals a mechanism governing T cell expansion, signal-dependent mRNA degradation induction and the potential in vivo biological significance of ac4C modification in T cell-mediated immune responses. The authors show that NAT10 is upregulated with T cell antigen receptor signaling and that T cell-specific NAT10 deficiency results in diminished numbers of naive T cells, translating to an inability to mount a significant antiviral T cell response.
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         name:Department of Emergency Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
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      address:
         name:Jinshan Hospital Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
         type:PostalAddress
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      address:
         name:Shanghai Key Laboratory of Lung Inflammation and Injury, Zhongshan Hospital, Fudan University, Shanghai, China
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            address:
               name:Shanghai Key Laboratory of Lung Inflammation and Injury, Zhongshan Hospital, Fudan University, Shanghai, China
               type:PostalAddress
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            address:
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      name:Xiaoyan Li
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            name:Shanghai Jiaotong University School of Medicine
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            address:
               name:Department of Emergency Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
               type:PostalAddress
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      name:Yuwen Chen
      affiliation:
            name:Fudan University
            address:
               name:Jinshan Hospital Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
               type:PostalAddress
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      affiliation:
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            address:
               name:Jinshan Hospital Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
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      name:Zhicheng Yang
      affiliation:
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            address:
               name:Jinshan Hospital Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
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      name:Ying Yang
      affiliation:
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            address:
               name:Jinshan Hospital Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
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      name:Ke Wang
      affiliation:
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            address:
               name:Jinshan Hospital Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
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      name:Tianyi Ren
      affiliation:
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            address:
               name:Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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      affiliation:
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            address:
               name:Jinshan Hospital Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
               type:PostalAddress
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      name:Hua Wang
      url:http://orcid.org/0000-0002-2605-5697
      affiliation:
            name:The First Affiliated Hospital of Anhui Medical University
            address:
               name:Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
               type:PostalAddress
            type:Organization
      name:Xiangdong Wang
      affiliation:
            name:Fudan University
            address:
               name:Shanghai Key Laboratory of Lung Inflammation and Injury, Zhongshan Hospital, Fudan University, Shanghai, China
               type:PostalAddress
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      name:Yan Lu
      url:http://orcid.org/0000-0003-3468-2241
      affiliation:
            name:Shanghai Jiao Tong University School of Medicine
            address:
               name:Institute of Metabolism and Regenerative Medicine, Digestive Endoscopic Center, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
               type:PostalAddress
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      email:[email protected]
      name:Zhenju Song
      url:http://orcid.org/0000-0001-9294-8824
      affiliation:
            name:Fudan University
            address:
               name:Shanghai Key Laboratory of Lung Inflammation and Injury, Zhongshan Hospital, Fudan University, Shanghai, China
               type:PostalAddress
            type:Organization
            name:Fudan University
            address:
               name:Department of Emergency Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Zhou-Li Cheng
      url:http://orcid.org/0009-0002-1961-534X
      affiliation:
            name:Fudan University
            address:
               name:Jinshan Hospital Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Duojiao Wu
      url:http://orcid.org/0000-0003-2562-8825
      affiliation:
            name:Fudan University
            address:
               name:Shanghai Key Laboratory of Lung Inflammation and Injury, Zhongshan Hospital, Fudan University, Shanghai, China
               type:PostalAddress
            type:Organization
            name:Fudan University
            address:
               name:Jinshan Hospital Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Shanghai Key Laboratory of Lung Inflammation and Injury, Zhongshan Hospital, Fudan University, Shanghai, China
      name:Department of Medical Oncology, Shanghai Cancer Center & Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
      name:Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
      name:Department of Geriatrics, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
      name:Department of Emergency Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
      name:Jinshan Hospital Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
      name:Jinshan Hospital Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
      name:Jinshan Hospital Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
      name:Jinshan Hospital Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
      name:Jinshan Hospital Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
      name:Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
      name:Jinshan Hospital Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
      name:Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
      name:Shanghai Key Laboratory of Lung Inflammation and Injury, Zhongshan Hospital, Fudan University, Shanghai, China
      name:Institute of Metabolism and Regenerative Medicine, Digestive Endoscopic Center, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
      name:Shanghai Key Laboratory of Lung Inflammation and Injury, Zhongshan Hospital, Fudan University, Shanghai, China
      name:Department of Emergency Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
      name:Jinshan Hospital Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
      name:Shanghai Key Laboratory of Lung Inflammation and Injury, Zhongshan Hospital, Fudan University, Shanghai, China
      name:Jinshan Hospital Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China

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