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Alphavirus infection triggers selective cytoplasmic translocation of nuclear RBPs with moonlighting antiviral roles
Molecular Cell ( IF 14.5 ) Pub Date : 2024-12-11 , DOI: 10.1016/j.molcel.2024.11.015 Wael Kamel, Vincenzo Ruscica, Azman Embarc-Buh, Zaydah R. de Laurent, Manuel Garcia-Moreno, Yana Demyanenko, Richard J. Orton, Marko Noerenberg, Meghana Madhusudhan, Louisa Iselin, Aino I. Järvelin, Maximilian Hannan, Eduardo Kitano, Samantha Moore, Andres Merits, Ilan Davis, Shabaz Mohammed, Alfredo Castello
Molecular Cell ( IF 14.5 ) Pub Date : 2024-12-11 , DOI: 10.1016/j.molcel.2024.11.015 Wael Kamel, Vincenzo Ruscica, Azman Embarc-Buh, Zaydah R. de Laurent, Manuel Garcia-Moreno, Yana Demyanenko, Richard J. Orton, Marko Noerenberg, Meghana Madhusudhan, Louisa Iselin, Aino I. Järvelin, Maximilian Hannan, Eduardo Kitano, Samantha Moore, Andres Merits, Ilan Davis, Shabaz Mohammed, Alfredo Castello
RNA is a central molecule for viruses; however, the interactions that viral RNA (vRNA) establishes with the host cell is only starting to be elucidated. Here, we determine the ribonucleoprotein (RNP) composition of the prototypical arthropod-borne Sindbis virus (SINV). We show that SINV RNAs engage with hundreds of cellular proteins, including a group of nuclear RNA-binding proteins (RBPs) with unknown roles in infection. We demonstrate that these nuclear RBPs are selectively translocated to the cytoplasm after infection, where they accumulate in the viral replication organelles (ROs). These nuclear RBPs strongly suppress viral gene expression, with activities spanning viral species and families. Particularly, the U2 small nuclear RNP (snRNP) emerges as an antiviral complex, with both its U2 small nuclear RNA (snRNA) and protein components contributing to the recognition of the vRNA and the antiviral phenotype. These results suggest that the U2 snRNP has RNA-driven antiviral activity in a mechanism reminiscent of the RNAi pathway.
中文翻译:
甲病毒感染触发具有兼职抗病毒作用的核 RBP 的选择性细胞质易位
RNA 是病毒的核心分子;然而,病毒 RNA (vRNA) 与宿主细胞建立的相互作用才刚刚开始阐明。在这里,我们确定了原型节肢动物传播的 Sindbis 病毒 (SINV) 的核糖核蛋白 (RNP) 组成。我们表明 SINV RNA 与数百种细胞蛋白结合,包括一组在感染中作用未知的核 RNA 结合蛋白 (RBP)。我们证明这些核 RBP 在感染后选择性地易位到细胞质,在那里它们在病毒复制细胞器 (RO) 中积累。这些核 RBP 强烈抑制病毒基因表达,其活性跨越病毒种类和家族。特别是,U2 小核 RNP (snRNP) 以抗病毒复合物的形式出现,其 U2 小核 RNA (snRNA) 和蛋白质成分都有助于识别 vRNA 和抗病毒表型。这些结果表明,U2 snRNP 具有 RNA 驱动的抗病毒活性,其机制让人想起 RNAi 通路。
更新日期:2024-12-11
中文翻译:
甲病毒感染触发具有兼职抗病毒作用的核 RBP 的选择性细胞质易位
RNA 是病毒的核心分子;然而,病毒 RNA (vRNA) 与宿主细胞建立的相互作用才刚刚开始阐明。在这里,我们确定了原型节肢动物传播的 Sindbis 病毒 (SINV) 的核糖核蛋白 (RNP) 组成。我们表明 SINV RNA 与数百种细胞蛋白结合,包括一组在感染中作用未知的核 RNA 结合蛋白 (RBP)。我们证明这些核 RBP 在感染后选择性地易位到细胞质,在那里它们在病毒复制细胞器 (RO) 中积累。这些核 RBP 强烈抑制病毒基因表达,其活性跨越病毒种类和家族。特别是,U2 小核 RNP (snRNP) 以抗病毒复合物的形式出现,其 U2 小核 RNA (snRNA) 和蛋白质成分都有助于识别 vRNA 和抗病毒表型。这些结果表明,U2 snRNP 具有 RNA 驱动的抗病毒活性,其机制让人想起 RNAi 通路。