m6A RNA Methylation Mediates the Immune Gene Regulatory Mechanism in Sebastes schlegelii Against Edwardsiella piscicida Infection.

Edwardsiella piscicida is a major pathogen in mariculture. The role of epitranscriptomic regulation in fish mucosal immunity remains unclear. We employed MeRIP-seq and RNA-seq to investigate m6A modifications in Sebastes schlegelii during E. piscicida infection. We identified 6523-7361 differential m6A peaks, with a shift toward 3'UTRs. Transcriptome analysis revealed that 1279 DEGs were enriched in complement and cytokine pathways while inflammatory mediators were suppressed at 6 hpi. At 24 hpi, 579 DEGs sustained acute-phase responses and pathogen recognition. Notably, 77 continuously upregulated and 145 downregulated immune genes were identified. Temporal m6A dynamics indicated METTL3 suppressed early methylation, while ALKBH5 induction facilitated late demethylation. Region-specific m6A regulation was observed that 5'UTR demethylation activated C7, while 3'UTR methylation suppressed c-Jun. Functional analysis suggests m6A methylation suppresses inflammation, while demethylation enhances pathogen clearance via complement and antigen presentation pathways. This study reveals epitranscriptomic regulation in teleost immunity and suggests targets for disease-resistant aquaculture.