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N6-methyladenosine RNA modification suppresses antiviral innate sensing pathways via reshaping double-stranded RNA.
- Source :
- Nature Communications; 3/11/2021, Vol. 12 Issue 1, p1-16, 16p
- Publication Year :
- 2021
-
Abstract
- 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<superscript>6</superscript>-methyladenosine (m<superscript>6</superscript>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<superscript>6</superscript>A methyltransferase METTL3 translocates into the cytoplasm to increase m<superscript>6</superscript>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<superscript>6</superscript>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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 12
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- 149565214
- Full Text :
- https://doi.org/10.1038/s41467-021-21904-y