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多嘧啶 tract 结合蛋白通过与内部核糖体进入位点的相互作用调节肠道病毒 71 的翻译。

Polypyrimidine Tract-Binding Protein Regulates Enterovirus 71 Translation Through Interaction with the Internal Ribosomal Entry Site.

机构信息

Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming, 650118, China.

The State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China.

出版信息

Virol Sin. 2019 Feb;34(1):66-77. doi: 10.1007/s12250-019-00089-1. Epub 2019 Feb 22.

Abstract

Enterovirus 71 (EV71), a major causative agent of hand, foot, and mouth disease, has caused periodic infection outbreaks in children in the Asia-Pacific region. In order to describe the largely unknown life cycle of EV71, the molecular basis of its virus-host interactions must first be determined. The 5' untranslated region of EV71 contains a cloverleaf-like structure and internal ribosomal entry site (IRES), which play an important role in transcription and translation of viral protein. We found that polypyrimidine tract-binding protein 1 (PTB) bound to the IRES of EV71. RNA recognition motifs 1 and 2 of PTB were responsible for its binding to the EV71 IRES. Moreover, PTB protein was shuttled from nucleus to cytoplasm after EV71 infection. Additionally, IRES activity and viral protein production were inhibited by PTB knockdown. These results suggest that PTB interacts with the EV71 IRES, and positively regulates viral protein translation.

摘要

肠道病毒 71 型(EV71)是引起亚太地区儿童手足口病的主要病原体,曾导致周期性感染爆发。为了描述 EV71 这种人们知之甚少的生命周期,必须首先确定其病毒-宿主相互作用的分子基础。EV71 的 5'非翻译区包含一个三叶草状结构和内部核糖体进入位点(IRES),在病毒蛋白的转录和翻译中发挥重要作用。我们发现多嘧啶 tract 结合蛋白 1(PTB)与 EV71 的 IRES 结合。PTB 的 RNA 识别基序 1 和 2 负责其与 EV71 IRES 的结合。此外,EV71 感染后,PTB 蛋白从核内易位到细胞质。此外,IRES 活性和病毒蛋白的产生被 PTB 敲低所抑制。这些结果表明,PTB 与 EV71 IRES 相互作用,并正向调节病毒蛋白翻译。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7ee/6420576/e4f660dba421/12250_2019_89_Fig1_HTML.jpg

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