Understanding of viral replication through the interaction with coronavirus nsp1 and host proteins

通过与冠状病毒 nsp1 和宿主蛋白的相互作用了解病毒复制

• 批准号: 24790439
• 负责人: WATARU KAMITANI
• 金额: $ 2.83万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24790439/
• 关键词: ウイルス; RNA分解; ウイルス複製; RNA分解機構; 感染症; RNA; ヘリケース

Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of a newly emerged disease. Nsp1 binds to 40S ribosome subunits, which causes a translational shutoff in the cells expressing nsp1. The nsp1-40S complex further induces an endonucleolytic RNA cleavage near the 5'UTR of host mRNA, resulting in the promotion of RNA decay. However, the mechanism by which nsp1-induced RNA cleavage is unknown. We identified Upf1 as a binding partner of nsp1 by pulldown purification and mass spectrometry. Upf1 is a predominantly cytoplasmic RNA-binding protein that is essential for nonsense-mediated RNA decay pathway. Coimmunoprecipitation analyses in transfected cells confirmed a specific interaction between nsp1 and Upf1. Small interfering RNA-mediated knockdown of Upf1 resulted in suppression of nsp1-mediated RNA cleavage. Our data indicate a novel mechanism of host mRNA cleavage by SARA-CoV nsp1 protein.

严重急性呼吸综合征冠状病毒（SARS CoV）是一种新型的疾病的病原体。Nsp 1与40 S核糖体亚基结合，这导致表达Nsp 1的细胞中的翻译关闭。nsp 1 - 40 S复合物进一步诱导宿主mRNA的5 'UTR附近的核酸内切RNA切割，导致RNA降解的促进。然而，nsp 1诱导RNA切割的机制尚不清楚。我们确定Upf 1作为结合伴侣的nsp 1的下拉纯化和质谱。Upf 1是一种主要与细胞质RNA结合的蛋白，在无义介导的RNA降解途径中起重要作用。转染细胞的免疫共沉淀分析证实了nsp 1和Upf 1之间的特异性相互作用。小干扰RNA介导的Upf 1敲低导致抑制nsp 1介导的RNA切割。我们的数据表明了一种新的机制，宿主mRNA切割SARA-CoV nsp 1蛋白。

项目成果

Circumvention of the translational shut-off in cells infected with SARS coronavirus through the interaction of nsp1 with 5' UTR of viral mRNA

通过 nsp1 与病毒 mRNA 5 UTR 的相互作用，规避 SARS 冠状病毒感染细胞中的翻译关闭

• 发表时间: 2011
• 作者: Ebina H;Kanemura Y;Suzuki Y;Urata K;Misawa N;Koyanagi Y.;Tomohisa TANAKA
• 通讯作者: Tomohisa TANAKA

SARS-CoVのnsp1タンパク質と相互作用する宿主因子の探索

寻找与 SARS-CoV 的 nsp1 蛋白相互作用的宿主因子

• 发表时间: 2012
• 作者: Tanaka T;Kamitani W;DeDiego ML;Enjuanes L;Matusura Y;田中智久,松浦善治,神谷亘
• 通讯作者: 田中智久,松浦善治,神谷亘

SARS coronavirus binds to the viral 5’UTR that induces host specific shutoff and mRNA degradation promotion

SARS 冠状病毒与病毒 5’UTR 结合，诱导宿主特异性关闭和促进 mRNA 降解

• 发表时间: 2012
• 作者: Tanaka T;Kamitani W;DeDiego ML;Enjuanes L;Matusura Y;田中智久,松浦善治,神谷亘;田中智久,松浦善治,神谷亘;田中智久，松浦善治，神谷 亘
• 通讯作者: 田中智久，松浦善治，神谷 亘