G3BP1-dependent condensation of translationally inactive viral RNAs antagonizes infection.

G3BP1-dependent condensation of translationally inactive viral RNAs antagonizes infection.
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DOI:
10.1126/sciadv.adk8152
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发表时间:
2024-02-02
期刊:
影响因子:
13.6
通讯作者:
Parker, Roy
Parker, Roy
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Burke, James M.;Ratnayake, Oshani C.;Watkins, J. Monty;Perera, Rushika;Parker, Roy

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G3BP1是一种RNA结合蛋白,它将未翻译的信使RNA浓缩成应激颗粒(SGs)。多种病毒可使G3BP1失活,并且认为它通过SG增强的抗病毒信号传导来拮抗病毒复制。在此,我们表明G3BP1和应激颗粒通常都不会改变先天免疫途径的激活。相反,我们表明西尼罗河病毒、寨卡病毒和严重急性呼吸综合征冠状病毒2编码的RNA易于发生依赖于G3BP1的RNA浓缩,这种浓缩通过限制翻译起始而增强,并且与病毒复制细胞器的破坏和病毒RNA复制相关。我们表明这些病毒通过抑制G3BP蛋白的RNA浓缩功能、劫持eIF4A的RNA解浓缩活性和/或维持高效翻译来抵消其RNA基因组的浓缩。这些发现表明RNA浓缩可作为一种内在的抗病毒机制发挥作用,这解释了为什么许多病毒使G3BP蛋白失活,并提示应激颗粒可能是这种抗病毒机制的遗迹。 病毒RNA的依赖于G3BP1的浓缩是哺乳动物细胞中的一种内在抗病毒机制。
G3BP1 is an RNA binding protein that condenses untranslating messenger RNAs into stress granules (SGs). G3BP1 is inactivated by multiple viruses and is thought to antagonize viral replication by SG-enhanced antiviral signaling. Here, we show that neither G3BP1 nor SGs generally alter the activation of innate immune pathways. Instead, we show that the RNAs encoded by West Nile virus, Zika virus, and severe acute respiratory syndrome coronavirus 2 are prone to G3BP1-dependent RNA condensation, which is enhanced by limiting translation initiation and correlates with the disruption of viral replication organelles and viral RNA replication. We show that these viruses counteract condensation of their RNA genomes by inhibiting the RNA condensing function of G3BP proteins, hijacking the RNA decondensing activity of eIF4A, and/or maintaining efficient translation. These findings argue that RNA condensation can function as an intrinsic antiviral mechanism, which explains why many viruses inactivate G3BP proteins and suggests that SGs may have arisen as a vestige of this antiviral mechanism. G3BP1-dependent condensation of viral RNA is an intrinsic antiviral mechanism in mammalian cells.
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