中国科学技术大学王雪娟研究小组宣布他们探明了胞质ATR通过vimentin磷酸化调控PRRSV和EBOV复制细胞器组装。相关论文于2026年11月5日发表于《分子细胞生物学杂志》。

共济失调毛细血管扩张突变和Rad3相关（ATR）激酶是DNA损伤反应和复制应激公认的主调控因子。在本研究中，研究人员揭示了ATR一种出乎意料的保守作用：它通过波形蛋白磷酸化促进两种不同RNA病毒——一种动脉炎病毒和一种丝状病毒——的复制。急性药物抑制或敲低ATR可强烈抑制病毒复制，并显著减少作为这些不同病毒类别复制细胞器（ROs）的双膜囊泡和无膜凝聚体的形成。值得注意的是，尽管ATR在整个病毒生命周期中被招募到细胞质ROs，但它特异性作用于复制阶段，而不影响病毒的吸附、进入或释放。研究人员进一步表明，ATR在ROs内直接与波形蛋白相互作用并使其磷酸化，驱动波形蛋白重排并界定RO边界。机制上，ATR依赖性的波形蛋白Ser459磷酸化对于PRRSV和EBOV感染期间的RO形成不可或缺。总之，这些发现揭示了一条保守的ATR–波形蛋白信号轴，促进多种RNA病毒的RO生物发生，定义了细胞质ATR通过波形蛋白磷酸化协调膜结合型和无膜型复制区室组装的一种非经典功能。

附：英文原文

Title: Cytoplasmic ATR orchestrates PRRSV and EBOV replication organelle assembly via vimentin phosphorylation

Author: Xu, Chenchen, Xia, Yuanyuan, Cao, Zengguo, Xu, Xinyi, Xiang, Yuehao, Li, Fangxu, Li, Pengcheng, Chiu, Sandra, Cai, Gang, Wang, Xuejuan

Issue&Volume: 2026-11-05

Abstract: The ataxia telangiectasia-mutated and Rad3-related (ATR) kinase is a well-established master regulator of the DNA damage response and replication stress. In this study, we uncover an unexpected, conserved role of ATR in promoting the replication of two distinct RNA viruses—an arterivirus and a filovirus—through vimentin phosphorylation. Acute pharmacologic inhibition or knockdown of ATR robustly suppress viral replication and sharply reduce the formation of double-membrane vesicles and membrane-less condensates that serve as replication organelles (ROs) for these divergent viral classes. Notably, although ATR is recruited to cytoplasmic ROs throughout the viral life cycle, it acts specifically at the replication stage without affecting viral attachment, entry, or egress. We further show that ATR directly interacts with and phosphorylates vimentin within ROs, driving vimentin rearrangement and delineating RO boundaries. Mechanistically, ATR-dependent phosphorylation of vimentin at Ser459 is indispensable for RO formation during infection by both PRRSV and EBOV. Together, these findings reveal a conserved ATR–vimentin signaling axis that promotes RO biogenesis across diverse RNA viruses, defining a noncanonical function of cytoplasmic ATR in orchestrating the assembly of both membrane-bound and membrane-less replication compartments via vimentin phosphorylation.

DOI: 10.1093/jmcb/mjag025

Source: https://dx.doi.org/10.1093/jmcb/mjag025

期刊信息

Journal of Molecular Cell Biology：《分子细胞生物学报》，创刊于1936年。隶属于牛津大学出版社，最新IF：5.5

官方网址：https://academic.oup.com/jmcb?login=false

投稿链接：https://mc.manuscriptcentral.com/jmcb