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The RNA-dependent RNA polymerase of enterovirus A71 associates with ribosomal proteins and positively regulates protein translation.
RNA Biology ( IF 3.6 ) Pub Date : 2020-02-06 , DOI: 10.1080/15476286.2020.1722448
Kuo-Ming Lee,Chih-Ching Wu,Shang-En Wu,Ya-Han Lin,Li-Ting Wang,Chun-Ru Chang,Peng-Nien Huang,Shin-Ru Shih,Rei-Lin Kuo

Enteroviruses, which may cause neurological complications, have become a public health threat worldwide in recent years. Interactions between cellular proteins and enteroviral proteins could interfere with cellular biological processes to facilitate viral replication in infected cells. Enteroviral RNA-dependent RNA polymerase (RdRP), known as 3D protein, mainly functions as a replicase for viral RNA synthesis in infected cells. However, the 3D protein encoded by enterovirus A71 (EV-A71) could also interact with several cellular proteins to regulate cellular events and responses during infection. To globally investigate the functions of the EV-A71 3D protein in regulating biological processes in host cells, we performed immunoprecipitation coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify host proteins that may associate with the 3D protein. We found that the 3D protein interacts with factors involved in translation-related biological processes, including ribosomal proteins. In addition, polysome profiling analysis showed that the 3D protein cosediments with small and large subunits of ribosomes. We further discovered that the EV-A71 3D protein could enhance EV-A71 internal ribosome entry site (IRES)-dependent translation as well as cap-dependent translation. Collectively, this research demonstrated that the RNA polymerase encoded by EV-A71 could join a functional ribosomal complex and positively regulate viral and host translation.

中文翻译:

肠道病毒A71的RNA依赖性RNA聚合酶与核糖体蛋白缔合,并积极调节蛋白翻译。

近年来,可能引起神经系统并发症的肠病毒已成为全球范围内的公共卫生威胁。细胞蛋白和肠病毒蛋白之间的相互作用可能会干扰细胞生物学过程,从而促进病毒在感染细胞中的复制。肠病毒RNA依赖性RNA聚合酶(RdRP),称为3D蛋白,主要用作感染细胞中病毒RNA合成的复制酶。但是,由肠道病毒A71(EV-A71)编码的3D蛋白也可以与几种细胞蛋白相互作用,以调节感染期间的细胞事件和反应。为了全面研究EV-A71 3D蛋白在调控宿主细胞生物学过程中的功能,我们将免疫沉淀与液相色谱-串联质谱(LC-MS / MS)结合使用,以鉴定可能与3D蛋白相关的宿主蛋白。我们发现3D蛋白与翻译相关的生物学过程中涉及的因子相互作用,包括核糖体蛋白。此外,多核糖体谱分析表明3D蛋白具有核糖体的小亚基和大亚基。我们进一步发现,EV-A71 3D蛋白可以增强EV-A71内部核糖体进入位点(IRES)依赖性翻译以及帽依赖性翻译。总体而言,这项研究表明,EV-A71编码的RNA聚合酶可以加入功能性核糖体复合物,并积极调节病毒和宿主的翻译。我们发现3D蛋白与翻译相关的生物学过程中涉及的因子相互作用,包括核糖体蛋白。此外,多核糖体谱分析表明3D蛋白具有核糖体的小亚基和大亚基。我们进一步发现,EV-A71 3D蛋白可以增强EV-A71内部核糖体进入位点(IRES)依赖性翻译以及帽依赖性翻译。总体而言,这项研究表明,EV-A71编码的RNA聚合酶可以加入功能性核糖体复合物,并积极调节病毒和宿主的翻译。我们发现3D蛋白与翻译相关的生物学过程中涉及的因子相互作用,包括核糖体蛋白。此外,多核糖体谱分析表明3D蛋白具有核糖体的小亚基和大亚基。我们进一步发现,EV-A71 3D蛋白可以增强EV-A71内部核糖体进入位点(IRES)依赖性翻译以及帽依赖性翻译。总体而言,这项研究表明,EV-A71编码的RNA聚合酶可以加入功能性核糖体复合物,并积极调节病毒和宿主的翻译。我们进一步发现,EV-A71 3D蛋白可以增强EV-A71内部核糖体进入位点(IRES)依赖性翻译以及帽依赖性翻译。总体而言,这项研究表明,EV-A71编码的RNA聚合酶可以加入功能性核糖体复合物,并积极调节病毒和宿主的翻译。我们进一步发现,EV-A71 3D蛋白可以增强EV-A71内部核糖体进入位点(IRES)依赖性翻译以及帽依赖性翻译。总体而言,这项研究表明,EV-A71编码的RNA聚合酶可以加入功能性核糖体复合物,并积极调节病毒和宿主的翻译。
更新日期:2020-03-22
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