Summary 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. Graphical abstract Highlights • ChIRP-MS of SARS-CoV-2 RNA identifies viral RNA-host protein interaction networks • Comparative analysis identifies SARS-specific and multi-viral RNA-protein complexes • SARS-CoV-2 interactome-focused CRISPR screens reveal a broad antiviral response • Host mitochondria serve as a general organelle platform for anti-SARS-CoV-2 immunity Interrogation of SARS-CoV-2 RNA-host protein interaction networks by ChIRP-MS and CRISPR screens, in comparison with other human viruses such as flaviviruses, picornavirus, and rhinovirus, identifies complexes specific to SARS-CoV-2 infection and highlights the role of mitochondria in mediating antiviral immunity.
【저자키워드】 SARS-CoV-2, Mitochondria, CRISPR, RNA-binding proteins, RNA virus, host-pathogen interactions, ChIRP-MS, 【초록키워드】 pandemic, Immunity, Antiviral, SARS-COV-2 infection, Infection, antiviral activity, virus, anti-SARS-CoV-2, RNA, Protein, specificity, rhinovirus, Comparative analysis, Factors, pathway, CRISPR screen, SARS-CoV-2 RNA, RNA virus, antiviral immunity, platform, antiviral response, Interaction, integration, Therapeutic benefit, connection, Abstract, These data, host protein, protein interactions, organelle, CRISPR Screens, virus-induced cell death, Host, approach, physical, highlight, Seven, PROTECT, defined, identify, functional, majority, demonstrated, complexes, highlighting, global mortality, RNA-protein complex, the SARS-CoV-2, 【제목키워드】 protein interaction, functional,