Department of Microbiology and Immunology, National Cheng Kung University, 70101 Tainan, Taiwan.
Department of Medical Research, E-Da Hospital, I-Shou University, 824005 Kaohsiung, Taiwan.
Sci Adv. 2024 Nov 8;10(45):eadq0660. doi: 10.1126/sciadv.adq0660. Epub 2024 Nov 6.
RIG-I-like receptors (RLRs) are cytosolic RNA sensors critical for antiviral immunity. RLR activation is regulated by polyubiquitination and oligomerization following RNA binding. Yet, little is known about how RLRs exploit subcellular organelles to facilitate their posttranslational modifications and activation. Endosomal adaptor TAPE regulates the endosomal TLR and cytosolic RLR pathways. The potential interplay between RIG-I signaling and endosomes has been explored. Here, we report that endosomes act as platforms for facilitating RIG-I polyubiquitination and complex formation. RIG-I was translocated onto endosomes to form signaling complexes upon activation. Ablation of endosomes impaired RIG-I signaling to type I IFN activation. TAPE mediates the interaction and polyubiquitination of RIG-I and TRIM25. TAPE-deficient myeloid cells were defective in type I IFN activation upon RNA ligand and virus challenges. Myeloid TAPE deficiency increased the susceptibility to RNA virus infection in vivo. Our work reveals endosomes as signaling platforms for RIG-I activation and antiviral immunity.
RIG-I 样受体 (RLRs) 是细胞浆 RNA 传感器，对抗病毒免疫至关重要。RLR 的激活受 RNA 结合后的多泛素化和寡聚化调节。然而，对于 RLR 如何利用亚细胞细胞器来促进其翻译后修饰和激活，知之甚少。内体衔接蛋白 TAPE 调节内体 TLR 和细胞浆 RLR 途径。已经探索了 RIG-I 信号与内体之间的潜在相互作用。在这里，我们报告内体作为促进 RIG-I 多泛素化和复合物形成的平台。在激活时，RIG-I 被转运到内体上形成信号复合物。内体的缺失会损害 RIG-I 信号向 I 型 IFN 的激活。TAPE 介导 RIG-I 和 TRIM25 的相互作用和多泛素化。在 RNA 配体和病毒挑战时，缺乏 TAPE 的髓样细胞中 I 型 IFN 的激活缺陷。髓样细胞 TAPE 缺陷增加了体内 RNA 病毒感染的易感性。我们的工作揭示了内体作为 RIG-I 激活和抗病毒免疫的信号平台。
