| Abstrakt: |
Circular RNAs (circRNAs) are involved in various physiological and pathological processes in both vertebrates and invertebrates. However, most studies on circRNAs have focused on their roles as endogenous competitive RNAs. Here, we report a novel function of circRNA derived from the Fibrinogen-like protein 1 gene (circ-FGL1) that inhibits coelomocyte apoptosis via competing with the deubiquitinase AjOTUB1 to bind AjMyc in Apostichopus japonicus during Vibrio splendidus infection. The results showed that circ-FGL1 is significantly downregulated in coelomocytes of V. splendidus-induced A. japonicus and negatively regulates coelomocyte apoptosis through the AjBax-AjCyt c pathway. Mechanistically, the deubiquitinase AjOTUB1 and circ-FGL1 could interact with the transcription factor protein AjMyc in the same region with circ-FGL1/AjMyc having greater affinity. Under normal conditions, high levels of circ-FGL1 bind directly to AjMyc, inhibiting the deubiquitylation of AjMyc by AjOTUB1 and leading to the degradation of AjMyc. After V. splendidus infection, AjMyc disassociates from the depressed expression of circ-FGL1, promoting its deubiquitylation by binding to the induced deubiquitinase AjOTUB1 to inhibit its degradation. AjMyc is then transferred to nucleus and promotes the transcription of AjCyt c and AjBax to induce coelomocyte apoptosis. The new finding will expand our present outstanding on the functional role of circRNAs and suggests new therapeutic targets for the treatment of echinoderms during bacterial invasion. Author summary: Apostichopus japonicus, a sea cucumber belonging to the phylum Echinodermata, represents an exceptional model for scientific research due to its unique evolutionary position between invertebrates and vertebrates. As a class rich in active substances with significant nutritional and medicinal value, sea cucumbers face threats from various pathogens, especially skin ulcer syndrome infected by Vibrio splendidus, which have caused substantial economic losses in A. japonicus aquaculture. A. japonicus counteract pathogen invasion through innate immunity and programmed cell death. Apoptosis, in particular, is the predominant mechanism for regulating cell death in echinoderms and has important implications for pathogen-induced immune homeostasis. Here, we identified circ-FGL1 as an antiapoptotic circRNA and found that circ-FGL1 interacts preferentially with the AjMyc protein, leading to the promotion of AjMyc degradation via ubiquitination under the normal conditions. After V. splendidus infection, induced AjOTUB1, a deubiquitinase, interacts with AjMyc at the same region as circ-FGL1 and facilitates the deubiquitination of AjMyc. AjMyc is then transferred to the nucleus, where it promotes the transcription of AjCyt c/AjBax, ultimately inducing coelomocyte apoptosis. Our study offers potential new therapeutic targets for treating in echinoderms during bacterial invasion. [ABSTRACT FROM AUTHOR] |
