{"doi":"10.1101/2022.02.21.481223","title":"Discovery and functional interrogation of SARS-CoV-2 protein-RNA interactions","abstract":"The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. SARS-CoV-2 proteins expressed in human lung epithelial cells bind to 4773 unique host coding RNAs. Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. Conversely, NSP9 inhibits host gene expression by blocking mRNA export and dampens cytokine productions, including interleukin-1α/β. Our viral protein-RNA interactome provides a catalog of potential therapeutic targets and offers insight into the etiology of COVID-19 as a safeguard against future pandemics.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":299049,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9671,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":549995,"name":"Jasmine R. Mueller","orcid":"0000-0001-6236-8001","position":1,"is_corresponding":false},{"id":254053,"name":"En‐Ching Luo","orcid":"0000-0001-7941-4924","position":2,"is_corresponding":false},{"id":43217,"name":"Brian A. Yee","orcid":"0000-0001-5615-8550","position":3,"is_corresponding":false},{"id":287400,"name":"Danielle Schafer","orcid":null,"position":4,"is_corresponding":false},{"id":264300,"name":"Jonathan C. Schmok","orcid":"0000-0002-5173-902X","position":5,"is_corresponding":false},{"id":264298,"name":"Frederick E. Tan","orcid":"0000-0001-5493-2127","position":6,"is_corresponding":false},{"id":21632,"name":"Katherine Rothamel","orcid":"0000-0001-9896-485X","position":7,"is_corresponding":false},{"id":106541,"name":"Rachael N. McVicar","orcid":"0000-0003-4384-4142","position":8,"is_corresponding":false},{"id":106540,"name":"Elizabeth M. Kwong","orcid":null,"position":9,"is_corresponding":false},{"id":849579,"name":"Krysten L. Jones","orcid":"0000-0001-9194-6245","position":10,"is_corresponding":false},{"id":879732,"name":"Hsuan-Lin Her","orcid":"0000-0001-7691-3816","position":11,"is_corresponding":false},{"id":166310,"name":"Chun-Yuan Chen","orcid":"0000-0001-6212-2888","position":12,"is_corresponding":false},{"id":284762,"name":"Anthony Q. Vu","orcid":"0000-0001-8922-6409","position":13,"is_corresponding":false},{"id":236070,"name":"Wenhao Jin","orcid":"0000-0002-7885-3527","position":14,"is_corresponding":false},{"id":660020,"name":"Samuel S. Park","orcid":"0000-0002-9230-7661","position":15,"is_corresponding":false},{"id":848012,"name":"Phuong Le","orcid":"0000-0003-1836-7145","position":16,"is_corresponding":false},{"id":461477,"name":"Kristopher W. Brannan","orcid":"0000-0002-0316-898X","position":17,"is_corresponding":false},{"id":80490,"name":"Eric Kofman","orcid":"0000-0001-5462-9099","position":18,"is_corresponding":false},{"id":988502,"name":"Yanhua Li","orcid":"0000-0002-6111-8331","position":19,"is_corresponding":false},{"id":625325,"name":"Alexandra Tankka","orcid":"0000-0003-3337-5725","position":20,"is_corresponding":false},{"id":461478,"name":"Kevin Dong","orcid":"0000-0002-2341-8472","position":21,"is_corresponding":false},{"id":988503,"name":"Yan Song","orcid":"0000-0003-2049-0214","position":22,"is_corresponding":false},{"id":103778,"name":"Aaron F. Carlin","orcid":"0000-0002-1669-8066","position":23,"is_corresponding":false},{"id":43186,"name":"Eric L. Van Nostrand","orcid":"0000-0002-5188-0082","position":24,"is_corresponding":false},{"id":106558,"name":"Sandra L. Leibel","orcid":"0000-0001-6867-2477","position":25,"is_corresponding":false},{"id":43290,"name":"G Yeo","orcid":null,"position":26,"is_corresponding":false},{"id":567103,"name":"Joy S. Xiang","orcid":"0000-0002-6400-1876","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T00:31:40.528568Z","pmid":"35233578","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":[]}