Figure 3.

Dendritic cells are regulated by m6A modifications through different mechanisms. (A) METTL14 depletion inhibited viral reproduction and promoted dsDNA- or HCMV-induced IFNB1 mRNA accumulation. (B) Downregulation of ALBKH5 in DCs increased m6A modifications on OGDH mRNA and reduced its mRNA stability and protein expression, thereby inhibiting viral replication. (C) The RNA helicase DDX46 demethylates the antiviral proteins MAVS, TRAF3 and TRAF6 by recruiting ALBKH5. (D) hnRNPA2B1 recognizes viral DNA and facilitates m6A modification nucleocytoplasmic trafficking of CGAS, IFI16, and STING mRNAs by preventing FTO-mediated demethylation. (E) Mettl3-specific depletion in DCs results in delayed maturation in response to lipopolysaccharide (LPS) and impaired phenotypic and functional maturation of DCs. Mechanistically, the expression of the costimulatory molecules CD40 and CD80, the TLR4 signaling adaptor Tirap and the cytokine IL-12 decreased with a low capacity to stimulate T-cell responses.