hnRNP A1 Interacts with the 5′ Untranslated Regions of Enterovirus 71 and Sindbis Virus RNA and Is Required for Viral Replication
hnRNP A1 Interacts with the 5′ Untranslated Regions of Enterovirus 71 and Sindbis Virus RNA and Is Required for Viral Replication
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DOI：
10.1128/jvi.02476-08
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发表时间：
2009-06-15
影响因子：
5.4
通讯作者：
Li, Mei-Ling
中科院分区：
文献类型：
--
作者：
Lin, Jing-Yi;Shih, Shin-Ru;Li, Mei-Ling
异质核核糖核蛋白（hnRNP）A1参与前体mRNA在细胞核中的剪接和在细胞质中的翻译调节。在病毒感染和细胞应激过程中，hnRNPA1在细胞质中的重新分布是一个受调节的过程。在这里，我们证明，hnRNP A1不仅是一个内部核糖体进入位点（IRES）的反式作用因子，特异性结合肠道病毒71（EV71）的5'非翻译区（UTR），并调节IRES依赖的翻译，但也结合辛德毕斯病毒（SV）的5'非翻译区，并促进其翻译。hnRNP A1在EV 71感染细胞中的胞浆重定位导致EV 71 IRES介导的翻译增强，并且其功能可以被hnRNP A2替代，而SV感染后hnRNP A1的胞浆重定位增强SV翻译，但是该功能不能被hnRNP A2替代。我们的研究提供了第一个直接的证据，hnRNP A1的细胞质重定位控制不仅IRES依赖，但也非IRES依赖的RNA病毒的翻译起始。
Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is involved in pre-mRNA splicing in the nucleus and translational regulation in the cytoplasm. The cytoplasmic redistribution of hnRNP A1 is a regulated process during viral infection and cellular stress. Here we demonstrate that hnRNP A1 not only is an internal ribosome entry site (IRES) trans-acting factor that binds specifically to the 5' untranslated region (UTR) of enterovirus 71 (EV71) and regulates IRES-dependent translation but also binds to the 5' UTR of Sindbis virus (SV) and facilitates its translation. The cytoplasmic relocalization of hnRNP A1 in EV71-infected cells leads to the enhancement of EV71 IRES-mediated translation, and its function can be substituted by hnRNP A2, whereas the cytoplasmic relocalization of hnRNP A1 following SV infection enhances the SV translation, but this function cannot be replaced by hnRNP A2. Our study provides the first direct evidence that the cytoplasmic relocalization of hnRNP A1 controls not only the IRES-dependent but also non-IRES-dependent translation initiations of RNA viruses.