Key Points Zebrafish RBM47 negatively regulates RLR-mediated IFN production. RBM47 interacts with and degrades MAVS in a lysosome-dependent manner. IFN is essential for hosts to defend against viral invasion, whereas it must be tightly regulated to prevent hyperimmune responses. Fish mitochondrial antiviral signaling protein (MAVS) is a vital factor for IFN production, but until now, there have been few studies on the regulation mechanisms of fish MAVS enabling IFN to be properly controlled. In this study, we show that zebrafish RNA-binding motif protein 47 (RBM47) promotes MAVS degradation in a lysosome-dependent manner to suppress IFN production. First, the transcription of IFN activated by polyinosinic/polycytidylic acid (poly I:C), spring viremia of carp virus, or retinoic acid–inducible gene I (RIG-I)–like receptor pathway components were significantly suppressed by RBM47. Second, RBM47 interacted with MAVS and promoted lysosome-dependent degradation of MAVS, changing the cellular location of MAVS from the cytoplasm to the lysosome region. Finally, RBM47 inhibited downstream MITA and IRF3/7 activation, impairing the host antiviral response. Collectively, these data suggest that zebrafish RBM47 negatively regulates IFN production by promoting lysosome-dependent degradation of MAVS, providing insights into the role of RBM47 in the innate antiviral immune response in fish.

中文翻译：

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斑马鱼 RBM47 促进 MAVS 的溶酶体依赖性降解以抑制 IFN 诱导

要点 斑马鱼 RBM47 负向调节 RLR 介导的 IFN 产生。RBM47 以依赖溶酶体的方式与 MAVS 相互作用并降解。干扰素对于宿主抵御病毒入侵是必不可少的，而它必须受到严格监管以防止超免疫反应。鱼类线粒体抗病毒信号蛋白（MAVS）是干扰素产生的重要因素，但迄今为止，关于鱼类MAVS使干扰素得到适当控制的调控机制的研究很少。在这项研究中，我们表明斑马鱼 RNA 结合基序蛋白 47 (RBM47) 以依赖溶酶体的方式促进 MAVS 降解，以抑制 IFN 的产生。一是聚肌苷酸/聚胞苷酸（poly I:C）激活的IFN转录，鲤鱼病毒春季病毒血症，或视黄酸诱导基因 I (RIG-I) 样受体通路组分被 RBM47 显着抑制。其次，RBM47与MAVS相互作用并促进MAVS的溶酶体依赖性降解，将MAVS的细胞位置从细胞质改变到溶酶体区域。最后，RBM47 抑制下游 MITA 和 IRF3/7 激活，削弱宿主抗病毒反应。总的来说，这些数据表明斑马鱼 RBM47 通过促进 MAVS 的溶酶体依赖性降解来负向调节 IFN 的产生，从而深入了解 RBM47 在鱼类先天抗病毒免疫反应中的作用。RBM47 抑制下游 MITA 和 IRF3/7 的激活，从而削弱宿主的抗病毒反应。总的来说，这些数据表明斑马鱼 RBM47 通过促进 MAVS 的溶酶体依赖性降解来负向调节 IFN 的产生，从而深入了解 RBM47 在鱼类先天抗病毒免疫反应中的作用。RBM47 抑制下游 MITA 和 IRF3/7 的激活，从而削弱宿主的抗病毒反应。总的来说，这些数据表明斑马鱼 RBM47 通过促进 MAVS 的溶酶体依赖性降解来负向调节 IFN 的产生，从而深入了解 RBM47 在鱼类先天抗病毒免疫反应中的作用。