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微小RNA-92a通过靶向维甲酸诱导基因-I抑制巨噬细胞的抗病毒反应。

MicroRNA-92a inhibits macrophage antiviral response by targeting retinoic acid inducible gene-I.

作者信息

Sheng Yuanjian, Wang Yong, Lu Wei, Zhou Yunlian, Dong Guijuan, Ge Xiaoxing, Song Yinjing, Zhang Yuanyuan

机构信息

Children's Hospital, Zhejiang University School of Medicine, No. 3333 Binsheng Road Hangzhou 310003, Zhejiang, China.

Department of Pediatric Dentistry, Beijing Stomatological Hospital and School of Stomatology, Capital Medical University, No. 4 Tian Tanxili, Beijing 100050, China.

出版信息

Microbiol Immunol. 2018 Sep;62(9):585-593. doi: 10.1111/1348-0421.12640.

Abstract

MicroRNAs are short, non-coding RNAs that have been shown to regulate a wide range of biological processes, including host antiviral immune responses. In the present study, microRNA-92a (miR-92a) was identified as a negative regulator in macrophage-mediated antiviral responses. Overexpression of miR-92a decreases vesicular stomatitis virus (VSV)-induced production of type-I IFNs and facilitates viral replication in macrophages. The mechanism is that miR-92a directly targets RIG-I and reduces its expression, thereby attenuating VSV-triggered activation of TBK-binding kinase 1 and IRF3, both of which are crucial for initiating transcription of type-I IFN genes. Our results demonstrate for the first time the novel role of miR-92a in suppressing antiviral innate immunity.

摘要

微小RNA是短链非编码RNA,已被证明可调节广泛的生物学过程,包括宿主抗病毒免疫反应。在本研究中,微小RNA-92a(miR-92a)被鉴定为巨噬细胞介导的抗病毒反应中的负调节因子。miR-92a的过表达降低了水泡性口炎病毒(VSV)诱导的I型干扰素的产生,并促进了病毒在巨噬细胞中的复制。其机制是miR-92a直接靶向维甲酸诱导基因I(RIG-I)并降低其表达,从而减弱VSV触发的TBK结合激酶1和干扰素调节因子3(IRF3)的激活,这两者对于启动I型干扰素基因的转录至关重要。我们的结果首次证明了miR-92a在抑制抗病毒先天免疫中的新作用。

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