Figure 3.

m⁶A modification participates in innate immunity via regulating the recognitions of unmodified transcribed RNA (tRNA), invading pathogens, exogenous RNAs, and aberrant endogenous double-stranded RNA (dsRNA). (A) m⁶A-modified tRNA reduces or eliminates the TLR3, TLR7, or TLR8 activation in monocyte-derived DCs (MDDCs). (B) m⁶A-methylation favors virion RNA escaping from the innate immunity recognitions in Huh7 cells and A549 cells. (C) Exogenous circRNAs, which lack m⁶A modifications, can be recognized by RIG-I signaling pathway in Hela cells. (D) Aberrant endogenous dsRNA in hematopoietic stem cells, which is formed by loss of m⁶A addition in ssRNA, can be recognized by RIG-I as foreign dsRNA and subsequently trigger a deleterious innate immune response. TLR3, Toll-like receptor 3; TLR7, Toll-like receptor 7; TLR8, Toll-like receptor 8; tRNA, transcribed RNA; RIG-I, retinoic acid-inducible gene I; MAVS, mitochondrial antiviral signaling protein; IRF3, interferon regulatory transcription factor 3; ssRNA, single-stranded RNA; dsRNA, double-stranded RNA; OAS, 2',5'-oligoadenylate synthetase gene; PKR, protein kinase R.