CircDDX17 enhances CVB3 replication by N6-methyladenosine regulation through miR-1248/NOTCH2 targeting

Abstract

N6-methyladenosine (m6A) is the most prevalent internal mRNA modification in eukaryotes. m6A is necessary for RNA metabolism and function, and influences RNA viruses replication. Methyltransferase-like protein 3 (METTL3) is a “writer” to regulating m6A. Coxsackievirus B3 (CVB3), belonging to the genus Enterovirus of the Picornaviridae family, are species of non-enveloped, positive single-stranded RNA virus. CVB3 infection reduces circular RNA_DDX17 (circDDX17) expression level in HeLa and HL-1 cells, as in viral myocarditis (VM). CircDDX17 enhanced CVB3 replication in HeLa and HL-1 cells and regulated NOTCH Receptor 2 (NOTCH2) by targeting microRNA-1248 (miR-1248) as microRNAs (miRNAs) sponge. NOTCH2 interaction with METTL3, through m6A proteins like methyltransferase-like protein 14 (METTL14), AlkB Homolog 5 (ALKBH5), and YTH N6-Methyladenosine RNA Binding Protein 1 (YTHDF1) to improve CVB3 replication in host cells. Taken together, this study suggests that circDDX17 targets miR-1248 to regulate NOTCH2 expression and regulates METTL3 to enhance CVB3 replication in cells by m6A relation protein.