Mettl3-mediated mRNA m6A methylation promotes dendritic cell activation

被引：427

作者：

Wang, Huamin ^{[1
,2
,3
,4
,5
]}

Hu, Xiang ^{[1
,2
,3
,4
,6
]}

Huang, Mingyan ^{[3
,4
]}

Liu, Juan ^{[3
,4
]}

Gu, Yan ^{[3
,4
]}

Ma, Lijia ^{[7
]}

Zhou, Qi ^{[8
]}

Cao, Xuetao ^{[1
,2
,3
,4
,5
,6
]}

机构：

[1] Chinese Acad Med Sci, Peking Union Med Coll, Inst Basic Med Sci, Dept Immunol, Beijing 100005, Peoples R China

[2] Chinese Acad Med Sci, Peking Union Med Coll, Inst Basic Med Sci, Ctr Immunotherapy, Beijing 100005, Peoples R China

[3] Second Mil Med Univ, Natl Key Lab Med Immunol, Shanghai 200433, Peoples R China

[4] Second Mil Med Univ, Inst Immunol, Shanghai 200433, Peoples R China

[5] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China

[6] Zhejiang Univ, Sch Med, Inst Immunol, Hangzhou 310058, Zhejiang, Peoples R China

[7] Westlake Inst Adv Study, Hangzhou 321116, Zhejiang, Peoples R China

[8] Chinese Acad Sci, Inst Zool, State Key Lab Reprod Biol, Beijing 100101, Peoples R China

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

中国国家自然科学基金;

关键词：

MOUSE; N-6-METHYLADENOSINE; TRANSLATION; REVEALS; N6-METHYLADENOSINE; RECOGNITION; IMMUNITY; SUBUNIT; BINDING;

D O I：

10.1038/s41467-019-09903-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

N6-methyladenosine (m(6)A) modification plays important roles in various cellular responses by regulating mRNA biology. However, how m(6)A modification is involved in innate immunity via affecting the translation of immune transcripts remains to be further investigated. Here we report that RNA methyltransferase Mettl3-mediated mRNA m(6)A methylation promotes dendritic cell (DC) activation and function. Specific depletion of Mettl3 in DC resulted in impaired phenotypic and functional maturation of DC, with decreased expression of costimulatory molecules CD40, CD80 and cytokine IL-12, and reduced ability to stimulate T cell responses both in vitro and in vivo. Mechanistically, Mettl3-mediated m(6)A of CD40, CD80 and TLR4 signaling adaptor Tirap transcripts enhanced their translation in DC for stimulating T cell activation, and strengthening TLR4/NF-kappa B signaling-induced cytokine production. Our findings identify a new role for Mettl3-mediated m(6)A modification in increasing translation of certain immune transcripts for physiological promotion of DC activation and DC-based T cell response.

引用

页数：12

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