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The RNA helicase DDX46 inhibits innate immunity by entrapping m6A-demethylated antiviral transcripts in the nucleus
Nature Immunology ( IF 30.5 ) Pub Date : 2017-08-28 00:00:00 , DOI: 10.1038/ni.3830
Qingliang Zheng , Jin Hou , Ye Zhou , Zhenyang Li , Xuetao Cao

DEAD-box (DDX) helicases are vital for the recognition of RNA and metabolism and are critical for the initiation of antiviral innate immunity. Modification of RNA is involved in many biological processes; however, its role in antiviral innate immunity has remained unclear. Here we found that nuclear DDX member DDX46 inhibited the production of type I interferons after viral infection. DDX46 bound Mavs, Traf3 and Traf6 transcripts (which encode signaling molecules involved in antiviral responses) via their conserved CCGGUU element. After viral infection, DDX46 recruited ALKBH5, an 'eraser' of the RNA modification N6-methyladenosine (m6A), via DDX46's DEAD helicase domain to demethylate those m6A-modified antiviral transcripts. It consequently enforced their retention in the nucleus and therefore prevented their translation and inhibited interferon production. DDX46 also suppressed antiviral innate immunity in vivo. Thus, DDX46 inhibits antiviral innate responses by entrapping selected antiviral transcripts in the nucleus by erasing their m6A modification, a modification normally required for export from the nucleus and translation.

中文翻译:

RNA解旋酶DDX46通过将m6A-去甲基化的抗病毒转录物截留在细胞核中来抑制先天免疫

DEAD-box(DDX)解旋酶对于RNA的识别和代谢至关重要,对于启动抗病毒先天免疫至关重要。RNA的修饰涉及许多生物学过程。然而,其在抗病毒先天免疫中的作用仍不清楚。在这里,我们发现核DDX成员DDX46抑制了病毒感染后I型干扰素的产生。DDX46通过保守的CCGGUU元件结合MavsTraf3Traf6转录本(编码参与抗病毒反应的信号分子)。病毒感染后,DDX46通过DDX46的DEAD解旋酶结构域募集ALKBH5 (RNA修饰N 6-甲基腺苷(m 6 A)的“橡皮擦” )使这些m 6去甲基化。A-修饰的抗病毒转录本。因此,它增强了它们在细胞核中的保留,因此阻止了它们的翻译并抑制了干扰素的产生。DDX46还抑制体内的抗病毒先天免疫。因此,DDX46通过擦除选择的抗病毒转录本的m 6 A修饰(通常是从细胞核输出和翻译所需的修饰),将选定的抗病毒转录本捕获在细胞核中,从而抑制了抗病毒的先天应答。
更新日期:2017-09-19
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