IGF2BP stabilizes RNF34 mRNA to orchestrate apoptosis and host susceptibility to Vibrio splendidus in Apostichopus japonicus

Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) are conserved N6-methyladenosine (m6A) readers known to orchestrate diverse host immune responses. However, its function in Apostichopus japonicus remains unclear during Vibrio splendidus Infection. In this study, we identified a single IGF2BP homolog (AjIGF2BP) in Apostichopus japonicus, which was markedly upregulated following Vibrio splendidus Infection. Functional analysis revealed that AjIGF2BP knockdown significantly reduced Bacterial load in coelomocytes and mitigated skin ulcer syndrome. Transcriptomic profiling revealed that AjIGF2BP knockdown significantly perturbed apoptotic pathways, among which the E3 ubiquitin Ligase ring finger protein 34 (AjRNF34) emerged as a strongly downregulated downstream effector. Mechanistically, AjIGF2BP directly bound to and stabilized AjRNF34 mRNA in an m6A-dependent manner. Rescue experiments confirmed that AjRNF34 was essential for the anti-apoptotic function of AjIGF2BP. Furthermore, AjRNF34 physically interacted with the executioner Caspase Ajcaspase-3 via its RING domain and promoted both K48-linked ubiquitination, facilitating its proteasomal degradation and thereby suppressing Apoptosis. Collectively, our findings unveil a novel AjIGF2BP/AjRNF34/Ajcaspase-3 regulatory axis through which m6A reader inhibits Apoptosis to facilitate Bacterial infection, offering new insights into the epigenetic regulatory mechanisms of immunity in echinoderms.

Apoptosis; Apostichopus japonicus; Insulin-like growth factor 2 mRNA-binding protein; Ring finger protein 34; Vibrio splendidus.