Global profiling reveals common and distinct N6-methyladenosine (m6A) regulation of innate immune responses during bacterial and viral infections

N(6)-methyladenosine (m(6)A) is a dynamic post-transcriptional RNA modification influencing all aspects of mRNA biology. While m(6)A modifications during numerous viral infections have been described, the role of m(6)A in innate immune response remains unclear. Here, we examined cellular m(6)A epitranscriptomes during infections of Pseudomonas aeruginosa and herpes simplex virus type 1 (HSV-1), and lipopolysaccharide (LPS) stimulation to identify m(6)A-regulated innate immune response genes. We showed that a significant portion of cellular genes including many innate immune response genes underwent m(6)A modifications in 5'UTR and 3'UTR. We identified common and distinct m(6)A-modified genes under different stimulating conditions. Significantly, the expression of a subset of innate immune response genes was positively correlated with m(6)A level. Importantly, we identified genes that had significant enrichments of m(6)A peaks during P. aeruginosa infection following knockdown of m(6)A “eraser” ALKBH5, confirming the regulation of these genes by m(6)A and ALKBH5. Among them, we confirmed the association of m(6)A modification with gene expression in immune response genes TNFAIP3, IFIT1, IFIT2 and IFIH1. Taken together, our results revealed the vital role of m(6)A in regulating innate immunity against bacterial and viral infections. These works also provided rich resources for the scientific community.