circMORC3-encoded novel protein negatively regulates antiviral immunity through synergizing with host gene MORC3

• Published in: PLoS pathogens Vol. 19; no. 12; p. e1011894
• Main Authors: Wang, Linchao, Zheng, Weiwei, Lv, Xing, Song, Yanhong, Xu, Tianjun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.12.2023; Public Library of Science (PLoS)
• Subjects: Amino acids; Analysis; Autophagy (Cytology); Biological response modifiers; Biology and Life Sciences; Circular RNA; Cytokines; Fish diseases; Gene expression; Genes; Health aspects; Infections; Innate immunity; Interferon; Interferon regulatory factor 3; Medicine and Health Sciences; NF-κB protein; Pathogens; Pattern recognition receptors; Peptides; Phosphorylation; Protein-protein interactions; Proteins; Research and Analysis Methods; RNA; RNA viruses; Signal transduction; Ubiquitin; Ubiquitination; Viral infections; China
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1011894

The protein-coding ability of circRNAs has recently been a hot topic, but the role of protein-coding circRNAs in antiviral innate immunity of teleost fish has rarely been reported. Here, we identified a novel circRNA, termed circMORC3, derived from Microrchidia 3 (MORC3) gene in Miichthys miiuy. circMORC3 can inhibit the expression of antiviral cytokines. In addition, circMORC3 encodes a novel peptide with a length of 84 amino acids termed MORC3-84aa. MORC3-84aa not only significantly inhibited TRIF-mediated activation of IRF3 and NF-κB signaling pathways, but also effectively suppressed the expression of antiviral cytokines triggered by RNA virus Siniperca chuatsi rhabdovirus (SCRV). We found that MORC3-84aa directly interacted with TRIF and negatively regulated TRIF protein expression. In addition, host gene MORC3 attenuates SCRV-induced IFN and ISG expression. Mechanistically, MORC3-84aa promotes autophagic degradation of TRIF by enhancing K6-linked ubiquitination and inhibits TRIF-mediated activation of the type I interferon signaling pathway. And the host gene MORC3 not only repressed IRF3 protein expression but also inhibited IRF3 phosphorylation levels. Our study shows that circMORC3 and host gene MORC3 played a synergistic role in viral immune escape.