Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions

Abstract

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.

Cited by papers we hold 4

• Genome-wide bidirectional CRISPR screens identify mucins as host factors modulating SARS-CoV-2 infection · 2022
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• Long COVID: mechanisms, risk factors and recovery · 2022
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• Comprehensive mapping of SARS-CoV-2 interactions in vivo reveals functional virus-host interactions · 2021
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• The architecture of the SARS-CoV-2 RNA genome inside virion · 2021
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