SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to Suppress Host Defenses.
SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to Suppress Host Defenses.
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DOI：
10.1016/j.cell.2020.10.004
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发表时间：
2020-11-25
期刊：
影响因子：
64.5
通讯作者：
Guttman M
中科院分区：
文献类型：
--
作者：
Banerjee AK;Blanco MR;Bruce EA;Honson DD;Chen LM;Chow A;Bhat P;Ollikainen N;Quinodoz SA;Loney C;Thai J;Miller ZD;Lin AE;Schmidt MM;Stewart DG;Goldfarb D;De Lorenzo G;Rihn SJ;Voorhees RM;Botten JW;Majumdar D;Guttman M
严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)是最近发现的一种冠状病毒，会导致被称为冠状病毒病2019(新冠肺炎)的呼吸道疾病。尽管SARS-CoV-2的研究迫在眉睫，但我们对SARS-CoV-2致病的分子基础仍不完全了解。在这里，我们全面定义SARS-CoV-2蛋白与人类RNA之间的相互作用。NSP16结合到U1和U2剪接RNA的mRNA识别结构域，并在SARS-CoV-2感染时抑制整体mRNA剪接。NSP1在核糖体的mRNA进入通道中与18S核糖体RNA结合，导致感染时mRNA翻译的全局抑制。最后，NSP8和NSP9与信号识别颗粒中的7SL RNA结合，并在感染时干扰蛋白质向细胞膜的运输。破坏这些基本的细胞功能中的每一个都会抑制干扰素对病毒感染的反应。我们的结果揭示了SARS-CoV-2利用多管齐下的策略来对抗抑制宿主防御的基本细胞过程。NSP16结合U1/U2SnRNAs的mRNA识别结构域，破坏mRNA剪接，NSP1结合在核糖体的mRNA进入通道，干扰蛋白质的翻译，NSP8和NSP9结合信号识别颗粒，扰乱蛋白质的运输，这些蛋白质生产的中断抑制了感染SARS-CoV-2蛋白的干扰素反应，直接与宿主RNA作用，调节蛋白质生产的必要步骤，抑制干扰素反应。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified coronavirus that causes the respiratory disease known as coronavirus disease 2019 (COVID-19). Despite the urgent need, we still do not fully understand the molecular basis of SARS-CoV-2 pathogenesis. Here, we comprehensively define the interactions between SARS-CoV-2 proteins and human RNAs. NSP16 binds to the mRNA recognition domains of the U1 and U2 splicing RNAs and acts to suppress global mRNA splicing upon SARS-CoV-2 infection. NSP1 binds to 18S ribosomal RNA in the mRNA entry channel of the ribosome and leads to global inhibition of mRNA translation upon infection. Finally, NSP8 and NSP9 bind to the 7SL RNA in the signal recognition particle and interfere with protein trafficking to the cell membrane upon infection. Disruption of each of these essential cellular functions acts to suppress the interferon response to viral infection. Our results uncover a multipronged strategy utilized by SARS-CoV-2 to antagonize essential cellular processes to suppress host defenses. NSP16 binds mRNA recognition domains of U1/U2 snRNAs and disrupts mRNA splicing NSP1 binds in the mRNA entry channel of the ribosome to disrupt protein translation NSP8 and NSP9 bind the signal recognition particle and disrupt protein trafficking These disruptions of protein production suppress the interferon response to infection SARS-CoV-2 proteins directly engage host RNAs to dysregulate essential steps of protein production and suppress the interferon response.
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影响因子：
6.7
作者：
Decroly E;Debarnot C;Ferron F;Bouvet M;Coutard B;Imbert I;Gluais L;Papageorgiou N;Sharff A;Bricogne G;Ortiz-Lombardia M;Lescar J;Canard B
通讯作者：
Canard B
影响因子：
3.7
作者：
Brockway SM;Denison MR
通讯作者：
Denison MR
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
7.3
作者：
Hermann, Thomas
通讯作者：
Hermann, Thomas
影响因子：
64.8
作者：
Claret, FX;Hibi, M;Karin, M
通讯作者：
Karin, M