武漢大學陳明周組揭示小RNA病毒拮抗應激顆粒形成機制

2019年1月1日，學術期刊《Cell Discovery》在線發表了病毒學國家重點實驗室陳明周教授團隊的最新研究成果，論文題為SG formation relies on eIF4GI-G3BP interaction which is targeted bypicornavirus stress antagonists（《小RNA病毒通過靶向eIF4GI-G3BP相互作用拮抗應激顆粒形成》）。

該工作揭示了eIF4GI-G3BP相互作用調節應激顆粒（stress granule, SG）形成的分子機制。應激顆粒是細胞質中大量蛋白和RNA聚集形成的、無包膜的結構。SGs是一種宿主細胞產生的抗病毒細胞防禦反應，但很多病毒會抑制或改造SGs以便利病毒的複製。在前期的工作中，研究者們發現腸道病毒71型的蛋白酶2A抑制經典SGs (typical stress granules, tSGs)、誘導了非經典SGs（atypical stressgranules, aSGs）形成，從而證實了2A蛋白酶在病毒感染過程中調控SGs的功能。本研究中，研究人員進一步發現小RNA病毒的2A蛋白通過阻斷eIF4GI-G3BP相互作用，從而拮抗tSGs的形成。此研究成果為為深入探討其它病毒與SGs的相互作用機制提供了理論支持。

博士生楊小丹為該論文的第一作者，陳明周教授為通訊作者。該工作得到了科技部和國家自然科學基金的支持。

Abstract

Typical stress granules (tSGs) are stalled translation pre-initiation complex aggregations in the cytoplasm, and their formation is a common consequence of translation initiation inhibition under stress. We previously found that 2A protease of picornaviruses blocks tSG formation and induces atypical SG formation, but the molecular mechanism by which 2A inhibits tSG formation remains unclear. Here, we found that eukaryotic translation initiation factor 4 gamma1 (eIF4GI) is critical for tSG formation by interacting with Ras-GTPase-activating protein SH3-domain-binding protein (G3BP), and this interaction is mediated by aa 182–203 of eIF4GI and the RNA-binding domain of G3BP. Upon eIF4GI-G3BP interaction, eIF4GI can assemble into tSGs and rescue tSG formation. Finally, we found that 2A or L protein of picornaviruses blocks tSG formation by disrupting eIF4GI-G3BP interaction. Our findings provide the first evidence that eIF4GI-G3BP interaction is indispensable for tSG formation, and 2A or L protein of picornaviruses interferes eIF4GI-G3BP interaction, thereby blocking tSG formation.

來源：武漢大學

本期編輯：Tony

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