METTL3-mediated m6A methylation orchestrates mRNA stability and dsRNA contents to equilibrate γδ T1 and γδ T17 cells
Summary: γδ T cells make key contributions to tissue physiology and immunosurveillance through two main functionally distinct subsets, γδ T1 and γδ T17. m6A methylation plays critical roles in controlling numerous aspects of mRNA metabolism that govern mRNA turnover, gene expression, and cellular fu...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723006952 |
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| author | Zhiqiang Xiao Shanshan Wang Yixia Tian Wenkai Lv Hao Sheng Mingjie Zhan Qiongxiao Huang Zhanpeng Zhang Leqing Zhu Chuyun Zhu Hui Zhong Qiong Wen Zonghua Liu Jingyi Tan Yan Xu Meixiang Yang Yumei Liu Richard A. Flavell Quanli Yang Guangchao Cao Zhinan Yin |
| author_facet | Zhiqiang Xiao Shanshan Wang Yixia Tian Wenkai Lv Hao Sheng Mingjie Zhan Qiongxiao Huang Zhanpeng Zhang Leqing Zhu Chuyun Zhu Hui Zhong Qiong Wen Zonghua Liu Jingyi Tan Yan Xu Meixiang Yang Yumei Liu Richard A. Flavell Quanli Yang Guangchao Cao Zhinan Yin |
| author_sort | Zhiqiang Xiao |
| collection | DOAJ |
| description | Summary: γδ T cells make key contributions to tissue physiology and immunosurveillance through two main functionally distinct subsets, γδ T1 and γδ T17. m6A methylation plays critical roles in controlling numerous aspects of mRNA metabolism that govern mRNA turnover, gene expression, and cellular functional specialization; however, its role in γδ T cells remains less well understood. Here, we find that m6A methylation controls the functional specification of γδ T17 vs. γδ T1 cells. Mechanistically, m6A methylation prevents the formation of endogenous double-stranded RNAs and promotes the degradation of Stat1 transcripts, which converge to prevent over-activation of STAT1 signaling and ensuing inhibition of γδ T17. Deleting Mettl3, the key enzyme in the m6A methyltransferases complex, in γδ T cells reduces interleukin-17 (IL-17) production and ameliorates γδ T17-mediated psoriasis. In summary, our work shows that METTL3-mediated m6A methylation orchestrates mRNA stability and double-stranded RNA (dsRNA) contents to equilibrate γδ T1 and γδ T17 cells. |
| first_indexed | 2024-03-13T03:28:27Z |
| format | Article |
| id | doaj.art-852a2da5c3144cb09f291e322ea0a9d9 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-13T03:28:27Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-852a2da5c3144cb09f291e322ea0a9d92023-06-25T04:42:52ZengElsevierCell Reports2211-12472023-07-01427112684METTL3-mediated m6A methylation orchestrates mRNA stability and dsRNA contents to equilibrate γδ T1 and γδ T17 cellsZhiqiang Xiao0Shanshan Wang1Yixia Tian2Wenkai Lv3Hao Sheng4Mingjie Zhan5Qiongxiao Huang6Zhanpeng Zhang7Leqing Zhu8Chuyun Zhu9Hui Zhong10Qiong Wen11Zonghua Liu12Jingyi Tan13Yan Xu14Meixiang Yang15Yumei Liu16Richard A. Flavell17Quanli Yang18Guangchao Cao19Zhinan Yin20Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China; The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, ChinaGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China; The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, ChinaGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China; The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, ChinaGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China; The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, ChinaNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518172, ChinaGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China; The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, ChinaInstitute of Dermatology, Guangzhou Medical University, Guangzhou 510095, China; Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou 510095, ChinaThe First Affiliated Hospital, Faculty of Medical Science, Jinan University, Guangzhou 510632, ChinaThe Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; The First Affiliated Hospital, Faculty of Medical Science, Jinan University, Guangzhou 510632, ChinaGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China; The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, ChinaGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China; The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, ChinaGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China; The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, ChinaGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China; The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, ChinaGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China; The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, ChinaGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China; The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, ChinaGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China; The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, ChinaInstitute of Dermatology, Guangzhou Medical University, Guangzhou 510095, China; Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou 510095, China; Corresponding authorDepartment of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA; Corresponding authorGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China; The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Corresponding authorGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China; The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Corresponding authorGuangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, China; The Biomedical Translational Research Institute, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, China; Corresponding authorSummary: γδ T cells make key contributions to tissue physiology and immunosurveillance through two main functionally distinct subsets, γδ T1 and γδ T17. m6A methylation plays critical roles in controlling numerous aspects of mRNA metabolism that govern mRNA turnover, gene expression, and cellular functional specialization; however, its role in γδ T cells remains less well understood. Here, we find that m6A methylation controls the functional specification of γδ T17 vs. γδ T1 cells. Mechanistically, m6A methylation prevents the formation of endogenous double-stranded RNAs and promotes the degradation of Stat1 transcripts, which converge to prevent over-activation of STAT1 signaling and ensuing inhibition of γδ T17. Deleting Mettl3, the key enzyme in the m6A methyltransferases complex, in γδ T cells reduces interleukin-17 (IL-17) production and ameliorates γδ T17-mediated psoriasis. In summary, our work shows that METTL3-mediated m6A methylation orchestrates mRNA stability and double-stranded RNA (dsRNA) contents to equilibrate γδ T1 and γδ T17 cells.http://www.sciencedirect.com/science/article/pii/S2211124723006952CP: Molecular biologyCP: Immunology |
| spellingShingle | Zhiqiang Xiao Shanshan Wang Yixia Tian Wenkai Lv Hao Sheng Mingjie Zhan Qiongxiao Huang Zhanpeng Zhang Leqing Zhu Chuyun Zhu Hui Zhong Qiong Wen Zonghua Liu Jingyi Tan Yan Xu Meixiang Yang Yumei Liu Richard A. Flavell Quanli Yang Guangchao Cao Zhinan Yin METTL3-mediated m6A methylation orchestrates mRNA stability and dsRNA contents to equilibrate γδ T1 and γδ T17 cells Cell Reports CP: Molecular biology CP: Immunology |
| title | METTL3-mediated m6A methylation orchestrates mRNA stability and dsRNA contents to equilibrate γδ T1 and γδ T17 cells |
| title_full | METTL3-mediated m6A methylation orchestrates mRNA stability and dsRNA contents to equilibrate γδ T1 and γδ T17 cells |
| title_fullStr | METTL3-mediated m6A methylation orchestrates mRNA stability and dsRNA contents to equilibrate γδ T1 and γδ T17 cells |
| title_full_unstemmed | METTL3-mediated m6A methylation orchestrates mRNA stability and dsRNA contents to equilibrate γδ T1 and γδ T17 cells |
| title_short | METTL3-mediated m6A methylation orchestrates mRNA stability and dsRNA contents to equilibrate γδ T1 and γδ T17 cells |
| title_sort | mettl3 mediated m6a methylation orchestrates mrna stability and dsrna contents to equilibrate γδ t1 and γδ t17 cells |
| topic | CP: Molecular biology CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723006952 |
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