The role of methyltransferase-like 3 (METTL3) in immune response modulation in bivalve (Mytilus coruscus) during bacterial infection

Abstract

N⁶-methyladenosine (m6A) modification is a prevalent mRNA modification that regulates diverse biological processes in eukaryotes, including immune responses. While the role of m6A in mammalian immunity has been explored, its involvement in the immune defense of invertebrates, particularly marine bivalves which face constant pathogen challenges, remains largely unknown. Here, we investigated the function of methyltransferase-like 3 (METTL3), a key m6A "writer" enzyme, in the immune response of the marine bivalve Mytilus coruscus against Vibrio alginolyticus infection. M. coruscus METTL3 (McMETTL3) expression in the digestive gland increased (3-fold) after V. alginolyticus infection, coinciding with elevated m6A levels. Silencing McMETTL3 reduced both m6A levels and V. alginolyticus-induced apoptosis in digestive gland cells. In silico analysis identified a C1q-like protein family member (McC1QL) as a potential downstream target of McMETTL3, exhibiting an increase (7.2-fold) in m6A modification and an increase (1.5-fold) in expression during infection. Functional experiments confirmed that McC1QL knockdown inhibited McMETTL3-driven apoptosis (10.83 %). These findings demonstrate that METTL3 regulates apoptosis and immune responses in invertebrates via m6A modification of target genes like McC1QL. This study provides novel insights into the m6A-mediated immune regulation mechanisms in marine bivalves and may offer potential avenues for developing innovative disease control strategies in aquaculture.