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Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions.
Flynn, Ryan A; Belk, Julia A; Qi, Yanyan; Yasumoto, Yuki; Wei, Jin; Alfajaro, Mia Madel; Shi, Quanming; Mumbach, Maxwell R; Limaye, Aditi; DeWeirdt, Peter C; Schmitz, Cameron O; Parker, Kevin R; Woo, Elizabeth; Chang, Howard Y; Horvath, Tamas L; Carette, Jan E; Bertozzi, Carolyn R; Wilen, Craig B; Satpathy, Ansuman T.
  • Flynn RA; Stanford ChEM-H and Department of Chemistry, Stanford University, Stanford, CA, USA. Electronic address: ryan.flynn@childrens.harvard.edu.
  • Belk JA; Department of Computer Science, Stanford University, Stanford, CA, USA; Department of Pathology, Stanford University, Stanford, CA, USA.
  • Qi Y; Department of Pathology, Stanford University, Stanford, CA, USA.
  • Yasumoto Y; Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University, New Haven, CT, USA.
  • Wei J; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
  • Alfajaro MM; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
  • Shi Q; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
  • Mumbach MR; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
  • Limaye A; Department of Pathology, Stanford University, Stanford, CA, USA.
  • DeWeirdt PC; Genetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Schmitz CO; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
  • Parker KR; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
  • Woo E; Department of Neuroscience, Yale School of Medicine, New Haven, CT, USA.
  • Chang HY; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Horvath TL; Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University, New Haven, CT, USA.
  • Carette JE; Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
  • Bertozzi CR; Stanford ChEM-H and Department of Chemistry, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Wilen CB; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA. Electronic address: craig.wilen@yale.edu.
  • Satpathy AT; Department of Pathology, Stanford University, Stanford, CA, USA. Electronic address: satpathy@stanford.edu.
Cell ; 184(9): 2394-2411.e16, 2021 04 29.
Article in English | MEDLINE | ID: covidwho-1126769
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA, Viral / Host-Pathogen Interactions / SARS-CoV-2 Limits: Animals / Female / Humans / Male Language: English Journal: Cell Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA, Viral / Host-Pathogen Interactions / SARS-CoV-2 Limits: Animals / Female / Humans / Male Language: English Journal: Cell Year: 2021 Document Type: Article