生物
泛素连接酶
甲型流感病毒
核糖核酸
细胞生物学
先天免疫系统
病毒复制
钻机-I
下调和上调
干扰素
泛素
分子生物学
病毒学
病毒
基因
免疫系统
生物化学
遗传学
作者
Nila Roy Choudhury,Ivan Trus,Gregory Heikel,Magdalena Wołczyk,Jacek Szymański,Agnieszka Bolembach,Rute Maria Pinto,Nikki Smith,Maryia Trubitsyna,Eleanor Gaunt,Paul Digard,Gracjan Michlewski
摘要
The E3 ubiquitin ligase TRIM25 is a key factor in the innate immune response to RNA viruses. TRIM25 has been shown to play a role in the retinoic-acid-inducible gene-1 (RIG-I) pathway, which triggers expression of type 1 interferons upon viral infection. We and others have shown that TRIM25 is an RNA-binding protein; however, the role of TRIM25 RNA-binding in the innate immune response to RNA viruses is unclear. Here, we demonstrate that influenza A virus (IAV A/PR/8/34_NS1(R38A/K41A)) infection is inhibited by TRIM25. Surprisingly, previously identified RNA-binding deficient mutant TRIM25ΔRBD and E3 ubiquitin ligase mutant TRIM25ΔRING, which lack E3 ubiquitin ligase activity, still inhibited IAV replication. Furthermore, we show that in human-derived cultured cells, activation of the RIG-I/interferon type 1 pathway mediated by either an IAV-derived 5'-triphosphate RNA or by IAV itself does not require TRIM25 activity. Additionally, we present new evidence that instead of TRIM25 directly inhibiting IAV transcription it binds and destabilizes IAV mRNAs. Finally, we show that direct tethering of TRIM25 to RNA is sufficient to downregulate the targeted RNA. In summary, our results uncover a potential mechanism that TRIM25 uses to inhibit IAV infection and regulate RNA metabolism.
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