内部收益率3
坦克结合激酶1
翻译(生物学)
磷酸化
生物
信使核糖核酸
丝氨酸
免疫系统
病毒学
免疫
细胞生物学
先天免疫系统
干扰素
免疫学
蛋白激酶A
基因
遗传学
丝裂原活化蛋白激酶激酶
作者
Jingxuan Chen,Xuemei Wei,Xiao Wang,Tong Liu,Yangyang Zhao,Luoying Chen,Yue Luo,Hongqiang Du,Yunfei Li,Tongtong Liu,Lili Cao,Zhe Zhou,Zeming Zhang,Ling Liang,Lü Li,Xuhui Yan,Xuehui Zhang,Xuliang Deng,Guang Yang,Ping Yin,Jianlei Hao,Zhinan Yin,Fangtian You
出处
期刊:Cell Reports
[Elsevier]
日期:2022-02-01
卷期号:38 (7): 110373-110373
被引量:23
标识
DOI:10.1016/j.celrep.2022.110373
摘要
mRNA m6A modification is heavily involved in modulation of immune responses. However, its function in antiviral immunity is controversial, and how immune responses regulate m6A modification remains elusive. We here find TBK1, a key kinase of antiviral pathways, phosphorylates the core m6A methyltransferase METTL3 at serine 67. The phosphorylated METTL3 interacts with the translational complex, which is required for enhancing protein translation, thus facilitating antiviral responses. TBK1 also promotes METTL3 activation and m6A modification to stabilize IRF3 mRNA. Type I interferon (IFN) induction is severely impaired in METTL3-deficient cells. Mettl3fl/fl-lyz2-Cre mice are more susceptible to influenza A virus (IAV)-induced lethality than control mice. Consistently, Ythdf1-/- mice show higher mortality than wild-type mice due to decreased IRF3 expression and subsequently attenuated IFN production. Together, we demonstrate that innate signals activate METTL3 via TBK1, and METTL3-mediated m6A modification secures antiviral immunity by promoting mRNA stability and protein translation.
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