Stanford ChEM-H and Department of Chemistry, Stanford University, Stanford, CA, USA.
Department of Computer Science, Stanford University, Stanford, CA, USA; Department of Pathology, Stanford University, Stanford, CA, USA.
Cell. 2021 Apr 29;184(9):2394-2411.e16. doi: 10.1016/j.cell.2021.03.012. Epub 2021 Mar 11.
SARS-CoV-2 is the cause of a pandemic with growing global mortality. Using comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS), we identified 309 host proteins that bind the SARS-CoV-2 RNA during active infection. Integration of this data with ChIRP-MS data from three other RNA viruses defined viral specificity of RNA-host protein interactions. Targeted CRISPR screens revealed that the majority of functional RNA-binding proteins protect the host from virus-induced cell death, and comparative CRISPR screens across seven RNA viruses revealed shared and SARS-specific antiviral factors. Finally, by combining the RNA-centric approach and functional CRISPR screens, we demonstrated a physical and functional connection between SARS-CoV-2 and mitochondria, highlighting this organelle as a general platform for antiviral activity. Altogether, these data provide a comprehensive catalog of functional SARS-CoV-2 RNA-host protein interactions, which may inform studies to understand the host-virus interface and nominate host pathways that could be targeted for therapeutic benefit.
SARS-CoV-2 是一种具有全球死亡率不断上升的大流行病毒的病原体。通过使用质谱法（ChIRP-MS）对 RNA 结合蛋白进行全面鉴定，我们在活跃感染期间鉴定出了 309 种与 SARS-CoV-2 RNA 结合的宿主蛋白。将这些数据与来自其他三种 RNA 病毒的 ChIRP-MS 数据进行整合，确定了病毒与 RNA-宿主蛋白相互作用的特异性。靶向 CRISPR 筛选揭示了大多数功能性 RNA 结合蛋白可以保护宿主免受病毒诱导的细胞死亡，而在七种 RNA 病毒之间进行的比较性 CRISPR 筛选揭示了共同的和 SARS 特异性的抗病毒因子。最后，通过将 RNA 中心方法与功能性 CRISPR 筛选相结合，我们证明了 SARS-CoV-2 与线粒体之间存在物理和功能联系，突显了该细胞器作为抗病毒活性的通用平台。总而言之，这些数据提供了 SARS-CoV-2 功能性 RNA-宿主蛋白相互作用的综合目录，这可能有助于研究宿主-病毒界面，并提名可能成为治疗受益目标的宿主途径。
