{"doi":"10.1101/2020.10.06.327445","title":"Systematic discovery and functional interrogation of SARS-CoV-2 viral RNA-host protein interactions during infection","abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a pandemic with growing global mortality. There is an urgent need to understand the molecular pathways required for host infection and anti-viral immunity. 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 viral ChIRP-MS data from three other positive-sense RNA viruses defined pan-viral and SARS-CoV-2-specific host interactions. Functional interrogation of these factors with a genome-wide CRISPR screen revealed that the vast majority of viral RNA-binding proteins protect the host from virus-induced cell death, and we identified known and novel anti-viral proteins that regulate SARS-CoV-2 pathogenicity. Finally, our RNA-centric approach demonstrated a physical connection between SARS-CoV-2 RNA and host mitochondria, which we validated with functional and electron microscopy data, providing new insights into a more general virus-specific protein logic for mitochondrial interactions. Altogether, these data provide a comprehensive catalogue of SARS-CoV-2 RNA-host protein interactions, which may inform future studies to understand the mechanisms of viral pathogenesis, as well as nominate host pathways that could be targeted for therapeutic benefit. HIGHLIGHTS: · ChIRP-MS of SARS-CoV-2 RNA identifies a comprehensive viral RNA-host protein interaction network during infection across two species· Comparison to RNA-protein interaction networks with Zika virus, dengue virus, and rhinovirus identify SARS-CoV-2-specific and pan-viral RNA protein complexes and highlights distinct intracellular trafficking pathways· Intersection of ChIRP-MS and genome-wide CRISPR screens identify novel SARS-CoV-2-binding proteins with pro- and anti-viral function· Viral RNA-RNA and RNA-protein interactions reveal specific SARS-CoV-2-mediated mitochondrial dysfunction during infection.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":119048,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":30,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":262617,"name":"Julia A. Belk","orcid":"0000-0003-4724-6158","position":1,"is_corresponding":false},{"id":551915,"name":"Yanyan Qi","orcid":"0000-0003-0537-1540","position":2,"is_corresponding":false},{"id":107010,"name":"Yuki Yasumoto","orcid":"0000-0001-9882-4478","position":3,"is_corresponding":false},{"id":110482,"name":"Cameron O. Schmitz","orcid":"0000-0002-9078-3744","position":4,"is_corresponding":false},{"id":25403,"name":"Maxwell R. Mumbach","orcid":"0000-0002-5570-6663","position":5,"is_corresponding":false},{"id":552792,"name":"Aditi Limaye","orcid":"0000-0002-8878-8714","position":6,"is_corresponding":false},{"id":110474,"name":"Jin Wei","orcid":"0000-0002-2832-1610","position":7,"is_corresponding":false},{"id":107015,"name":"Mia Madel Alfajaro","orcid":"0000-0002-6402-2730","position":8,"is_corresponding":false},{"id":227858,"name":"Kevin R. Parker","orcid":"0000-0001-5532-238X","position":9,"is_corresponding":false},{"id":26,"name":"Howard Y. Chang","orcid":"0000-0002-9459-4393","position":10,"is_corresponding":false},{"id":107023,"name":"Tamás L. Horváth","orcid":"0000-0002-7522-4602","position":11,"is_corresponding":false},{"id":227957,"name":"Jan E. Carette","orcid":"0000-0002-5187-8070","position":12,"is_corresponding":false},{"id":218284,"name":"Carolyn R. Bertozzi","orcid":"0000-0003-4482-2754","position":13,"is_corresponding":false},{"id":107022,"name":"Craig B. Wilen","orcid":"0000-0003-2495-9403","position":14,"is_corresponding":false},{"id":21653,"name":"Ansuman T. Satpathy","orcid":"0000-0002-5167-537X","position":15,"is_corresponding":false},{"id":228591,"name":"Ryan A. Flynn","orcid":"0000-0001-5013-0442","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-18T23:14:03.409507Z","pmid":"33052334","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}