Mettl3-mediated mRNA m6A methylation promotes dendritic cell activation

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 methy...

Full description

Saved in:
Bibliographic Details
Published in:Nature communications 2019-04, Vol.10 (1), p.1898-1898, Article 1898
Main Authors: Wang, Huamin, Hu, Xiang, Huang, Mingyan, Liu, Juan, Gu, Yan, Ma, Lijia, Zhou, Qi, Cao, Xuetao
Format: Article
Language:English
Subjects:
49
49/91
631/250/21/1293
631/250/2502/2170
631/80/86
CD40 antigen
CD80 antigen
Cell activation
Cytokines
Dendritic cells
Dendritic structure
Depletion
Humanities and Social Sciences
Immunity
Innate immunity
Interleukin 12
Lymphocytes
Lymphocytes T
Methylation
multidisciplinary
N6-methyladenosine
NF-κB protein
Science
Science (multidisciplinary)
Signaling
TLR4 protein
Toll-like receptors
Translation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 co-stimulatory 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-κB 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. Here the authors examine how m 6 A modification is involved in innate immunity. They show that RNA methyltransferase Mettl3-mediated mRNA m 6 A methylation promotes dendritic cell (DC) activation and function, and in promoting DC-based T cells responses.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-019-09903-6