CircMETTL7A enhances Toll pathway-mediated innate immunity and antibacterial activity in V. splendidus-challenged Apostichopus japonicus by reducing miR-137 function

Abstract

Circular RNA (circRNA) is an endogenous noncoding RNA subgroup with covalently closed rings that are widely expressed. Over the past few years, growing data confirmed that circRNAs function as significant regulators involved in numerous biological processes. However, the biological functions and underlying immune mechanism of circRNAs upon bacterial infection in lower invertebrates are further unclarified. Here, we discovered a circRNA derived from the methyltransferase-like protein 7A (METTL7A) gene, named circMETTL7A, which is closely bound up with an antibacterial response in Apostichopus japonicus. The results indicated that circMETTL7A displayed a significant ability in host antibacterial immunity and inhibition of the pathogenic Vibrio splendidus invasion. Our results also identified a microRNA, miR-137, which could suppress the host antibacterial responses and enhance V. splendidus invasion by targeting A. japonicus Toll (AjToll). Moreover, we detected that the antibacterial effects and AjToll protein levels inhibited due to circMETTL7A knockdown can be reversed by supplementing with miR-137 inhibitors. Mechanically, our results presented that circMETTL7A acts as a ceRNA of AjToll by sponging miR-137, leading to initiation of the NF-κB pathway, and thus boosting the antibacterial immunity in A. japonicus. Our results provide new insights for understanding circRNA functions upon bacterial infection in echinoderms and enrich the data for disease prevention in A. japonicus breeding.