N6-Methyladenosine Modification Controls Circular RNA Immunity.

ABSTRACT: Circular RNAs (circRNAs) are prevalent in eukaryotic cells and viral genomes. Mammalian cells possess innate immunity to detect foreign circRNAs, but the molecular basis of self versus foreign identity in circRNA immunity is unknown. Here, we show that N6-methyladenosine (m⁶A) RNA modification on human circRNAs inhibits innate immunity. Foreign circRNAs are potent adjuvants to induce antigen-specific T cell activation, antibody production, and anti-tumor immunity in vivo, and m⁶A modification abrogates immune gene activation and adjuvant activity. m⁶A reader YTHDF2 sequesters m⁶A-circRNA and is essential for suppression of innate immunity. Unmodified circRNA, but not m⁶A-modified circRNA, directly activates RNA pattern recognition rece

SUBMITTER: Chen YG 

PROVIDER: S-EPMC6778039 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature