Figure 3:

The m⁶A RNA modification regulates circRNA immunity. In vitro-transcribed foreign circRNAs that lack m⁶A modifications are detected by the nucleic acid sensor RIG-I, which then stimulate an innate immune response. Endogenous circRNAs, transcribed and spliced by cellular machinery, possess m⁶A modifications and do not stimulate innate immunity due to detection and sequestration by m⁶A “reader” YTHDF2. m⁶A is also required for the translation of specific viral circRNAs into protein, as seen in HPV-encoded circE7.