WTAP, a conserved m6A writer, can promote the antiviral immunity of Miichthys miiuy

Abstract

N6-methyladenosine (m⁶A) is one of the most prevalent modifications found in eukaryotic mRNA and has been implicated in the regulation of cell proliferation, development, invasion, apoptosis, and immunity. In this study, we first conducted a structural and evolutionary analysis of Wilms' tumour 1-associating protein (WTAP) in vertebrates, and the results showed that WTAP in vertebrates is conserved particularly in mammals and fish. We subsequently investigated the involvement of WTAP in the antiviral immune response of fish and discovered that the expression of Miichthys miiuy (mmiWTAP) decreased in response to stimulation with Siniperca chuatsi rhabdovirus (SCRV) and poly(I:C). Immunofluorescence assays revealed that mmiWTAP was distributed in both the nucleus and the cytoplasm. Furthermore, overexpression of mmiWTAP enhanced the mRNA expression of MAVS and antiviral genes, thereby inhibiting SCRV replication. The beneficial effects of WTAP on MAVS and antiviral factors were disrupted upon introduction of cycloleucine, a methylation inhibitor, suggesting that the positive regulatory role of mmiWTAP in the antiviral immune response is reliant on its methyltransferase activity. These findings provide new insights into the involvement of m⁶A regulatory networks in fish antiviral immunity.