Details

Autor(en) / Beteiligte

• Qiu, Weinan
• Zhang, Qingyang
• Zhang, Rui
• Lu, Yangxu
• Wang, Xin
• Tian, Huabin
• Yang, Ying
• Gu, Zijuan
• Gao, Yanan
• Yang, Xin
• Cui, Guanshen
• Sun, Baofa
• Peng, Yanan
• Deng, Hongyu
• Peng, Hua
• Yang, Angang
• Yang, Yun-Gui
• Yang, Pengyuan

Titel

N 6 -methyladenosine RNA modification suppresses antiviral innate sensing pathways via reshaping double-stranded RNA

Ist Teil von

• Nature communications, 2021-03, Vol.12 (1), p.1582-16

Ort / Verlag

England: Nature Portfolio

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• Double-stranded RNA (dsRNA) is a virus-encoded signature capable of triggering intracellular Rig-like receptors (RLR) to activate antiviral signaling, but whether intercellular dsRNA structural reshaping mediated by the N -methyladenosine (m A) modification modulates this process remains largely unknown. Here, we show that, in response to infection by the RNA virus Vesicular Stomatitis Virus (VSV), the m A methyltransferase METTL3 translocates into the cytoplasm to increase m A modification on virus-derived transcripts and decrease viral dsRNA formation, thereby reducing virus-sensing efficacy by RLRs such as RIG-I and MDA5 and dampening antiviral immune signaling. Meanwhile, the genetic ablation of METTL3 in monocyte or hepatocyte causes enhanced type I IFN expression and accelerates VSV clearance. Our findings thus implicate METTL3-mediated m A RNA modification on viral RNAs as a negative regulator for innate sensing pathways of dsRNA, and also hint METTL3 as a potential therapeutic target for the modulation of anti-viral immunity.