Identification and characterization of host proteins bound to dengue virus 3' UTR reveal an antiviral role for quaking proteins.
Identification and characterization of host proteins bound to dengue virus 3' UTR reveal an antiviral role for quaking proteins.
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DOI：
10.1261/rna.064006.117
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Garcia-Blanco MA
中科院分区：
文献类型：
--
作者：
Liao KC;Chuo V;Ng WC;Neo SP;Pompon J;Gunaratne J;Ooi EE;Garcia-Blanco MA
四种登革热病毒（DENV1-4）是迅速重新出现的传染性RNA病毒。这些正链病毒基因组包含与各种宿主RNA结合蛋白（rbp）相互作用的结构3 '非翻译区（utr）。这些rbp在病毒复制、发病和防御宿主免疫机制中具有重要的功能。在这里，我们结合RNA色谱法和定量质谱法来鉴定与DENV1-4 3 ' utr相互作用的蛋白质。正如预期的那样，rbp表现出明显的结合特异性。其中，我们重点研究了地震（QKI），因为它偏爱DENV4 3 ' UTR （DENV-4/SG/06K2270DK1/2005）。RNA免疫沉淀实验表明，QKI与感染细胞中的DENV4基因组相互作用。QKI缺失增强了DENV4感染颗粒的产生。相反，QKI不与DENV2 3 ' UTR相互作用，并且QKI的缺失不一致地影响DENV2的复制。接下来，我们绘制了QKI相互作用位点，并在DENV4 3 ' UTR中确定了一个QKI应答元件（QRE）。有趣的是，从DENV4 3 ' UTR中去除QRE消除了这种相互作用，增加了DENV4病毒颗粒的产生。将QRE引入DENV2 3 ' UTR导致QKI结合并减少了DENV2感染性颗粒的产生。最后，报告者实验表明QKI降低了病毒RNA的翻译效率。我们的工作描述了QKI在限制病毒复制方面的一种新功能。
The four dengue viruses (DENV1-4) are rapidly reemerging infectious RNA viruses. These positive-strand viral genomes contain structured 3′ untranslated regions (UTRs) that interact with various host RNA binding proteins (RBPs). These RBPs are functionally important in viral replication, pathogenesis, and defense against host immune mechanisms. Here, we combined RNA chromatography and quantitative mass spectrometry to identify proteins interacting with DENV1-4 3′ UTRs. As expected, RBPs displayed distinct binding specificity. Among them, we focused on quaking (QKI) because of its preference for the DENV4 3′ UTR (DENV-4/SG/06K2270DK1/2005). RNA immunoprecipitation experiments demonstrated that QKI interacted with DENV4 genomes in infected cells. Moreover, QKI depletion enhanced infectious particle production of DENV4. On the contrary, QKI did not interact with DENV2 3′ UTR, and DENV2 replication was not affected consistently by QKI depletion. Next, we mapped the QKI interaction site and identified a QKI response element (QRE) in DENV4 3′ UTR. Interestingly, removal of QRE from DENV4 3′ UTR abolished this interaction and increased DENV4 viral particle production. Introduction of the QRE to DENV2 3′ UTR led to QKI binding and reduced DENV2 infectious particle production. Finally, reporter assays suggest that QKI reduced translation efficiency of viral RNA. Our work describes a novel function of QKI in restricting viral replication.
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影响因子：
64.5
作者：
Hafner M;Landthaler M;Burger L;Khorshid M;Hausser J;Berninger P;Rothballer A;Ascano M Jr;Jungkamp AC;Munschauer M;Ulrich A;Wardle GS;Dewell S;Zavolan M;Tuschl T
通讯作者：
Tuschl T
影响因子：
6.6
作者：
de Miguel, Fernando J.;Pajares, Maria J.;Pio, Ruben
通讯作者：
Pio, Ruben
DOI：
10.1073/pnas.0703348104
发表时间：
2007-05-22
影响因子：
11.1
作者：
Emara, Mohamed M.;Brinton, Margo A.
通讯作者：
Brinton, Margo A.
影响因子：
5.4
作者：
Chiu, WW;Kinney, RM;Dreher, TW
通讯作者：
Dreher, TW
影响因子：
5.4
作者：
Campos, Rafael K.;Wong, Benjamin;Bradrick, Shelton S.
通讯作者：
Bradrick, Shelton S.