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  2. Methyltransferase-Like Protein 14 Attenuates Mitochondrial Antiviral Signaling Protein Expression to Negatively Regulate Antiviral Immunity via N6 -methyladenosine Modification

Methyltransferase-Like Protein 14 Attenuates Mitochondrial Antiviral Signaling Protein Expression to Negatively Regulate Antiviral Immunity via N6 -methyladenosine Modification

  • Adv Sci (Weinh). 2021 Aug;8(15):e2100606. doi: 10.1002/advs.202100606.
Fei Qin 1 Baoshan Cai 1 Jian Zhao 1 Lei Zhang 1 Yi Zheng 1 Bingyu Liu 1 Chengjiang Gao 1
Affiliations

Affiliation

  • 1 Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Biomedical Sciences, Shandong University, Jinan, Shandong, 250012, P. R. China.
Abstract

Mitochondrial Antiviral signaling (MAVS) protein is the core signaling adaptor in the RNA signaling pathway. Thus, appropriate regulation of MAVS expression is essential for Antiviral immunity against RNA virus Infection. However, the regulation of MAVS expression at the mRNA level especially at the post transcriptional level is not well-defined. Here, it is reported that the MAVS mRNA undergoes N6 -methyladenosine (m6 A) modification through methyltransferase-like protein 14 (METTL14), which leads to a fast turnover of MAVS mRNA. Knockdown or deficiency of METTL14 increases MAVS mRNA stability, and downstream phosphorylation of TBK1/IRF3 and interferon-β production in response to RNA viruses. Compared to wild-type mice, heterozygotes Mettl14+/- mice better tolerate RNA virus Infection. The authors' findings unveil a novel mechanism to regulate the stability of MAVS transcripts post-transcriptionally through m6 A modification.

Keywords

N6-methyladenosine modification; antiviral immunity; mRNA stability; methyltransferase-like protein 14; mitochondrial antiviral signaling protein.

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