中国医学科学院曹雪涛小组的一项最新研究，揭示了长链非编码RNA Lnczc3h7a促进TRIM25介导的RIG-I抗病毒天然免疫应答。 这一研究成果于2019年7月发表在国际顶尖学术期刊《自然—免疫学》上。

研究人员鉴定了一种新的长链非编码RNA (Lnczc3h7a)，它与TRIM25结合，促进RIG-I 介导的抗病毒先天免疫反应。Lnczc3h7a的缺失破坏了RIG-I信号通路和体内外对RNA病毒的抗病毒固有免疫应答。机制上，Lnczc3h7a与TRIM25结合并活化RIG-I，作为病毒感染早期RIG-I - TRIM25复合物稳定的分子支架。Lnczc3h7a促进TRIM25介导的RIG-I K63连接泛素化，促进下游信号转导。研究结果表明，宿主RNA可以增强对外来RNA的固有免疫反应，确保有效的抗病毒防御。

据悉，解旋酶RIG-I在识别病原体RNA后启动抗病毒免疫应答。TRIM25 是一种E3泛素连接酶，介导RIG-I的K63连接泛素化，对RIG-I下游信号的传导和抗病毒先天免疫反应至关重要。RIG-I诱发的固有免疫信号通路的组件以及调节模式仍不完全清楚。

附：英文原文

Title: The long noncoding RNA Lnczc3h7a promotes a TRIM25-mediated RIG-I antiviral innate immune response

Author: Hongyu Lin, Minghong Jiang, Lun Liu, Zongheng Yang, Zhongfei Ma, Shuo Liu, Yuanwu Ma, Lianfeng Zhang, Xuetao Cao

Issue&Volume: Volume 20 Issue 7, July 2019

Abstract: The helicase RIG-I initiates an antiviral immune response after recognition of pathogenic RNA. TRIM25, an E3 ubiquitin ligase, mediates K63-linked ubiquitination of RIG-I, which is crucial for RIG-I downstream signaling and the antiviral innate immune response. The components and mode of the RIG-I-initiated innate signaling remain to be fully understood. Here we identify a novel long noncoding RNA (Lnczc3h7a) that binds to TRIM25 and promotes RIG-I-mediated antiviral innate immune responses. Depletion of Lnczc3h7a impairs RIG-I signaling and the antiviral innate response to RNA viruses in vitro and in vivo. Mechanistically, Lnczc3h7a binds to both TRIM25 and activated RIG-I, serving as a molecular scaffold for stabilization of the RIG-ITRIM25 complex at the early stage of viral infection. Lnczc3h7a facilitates TRIM25-mediated K63-linked ubiquitination of RIG-I and thus promotes downstream signaling transduction. Our findings reveal that host RNAs can enhance the response of innate immune sensors to foreign RNAs, ensuring effective antiviral defense.

DOI: 10.1038/s41590-019-0379-0

Source: https://www.nature.com/articles/s41590-019-0379-0