{"doi":"10.7554/elife.100248.1.sa1","title":"Reviewer #2 (Public Review): SARS-CoV-2 NSP13 interacts with TEAD to suppress Hippo-YAP signaling","abstract":"The Hippo pathway is critical to organ development, homeostasis, and regeneration, facilitated by YAP/TEAD-mediated gene expression. Although emerging studies report Hippo-YAP dysfunction after viral infection, it is largely unknown in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we analyzed RNA sequencing data from SARS-CoV-2 infected human lung samples and induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs), and observed a decrease in YAP target gene expression. In screening SARS-CoV-2 nonstructural proteins, we found that nonstructural protein 13 (NSP13), a conserved coronavirus helicase, inhibited YAP transcriptional activity independent of the upstream Hippo kinases LATS1/2. Consistently, introducing NSP13 into cardiomyocytes suppressed active YAP (YAP5SA) in vivo. Subsequent investigations on NSP13 mutants indicated that NSP13 helicase activity is crucial for suppressing YAP transactivation. Mechanistically, TEAD4 serves as a platform for recruiting NSP13 and YAP. NSP13 inactivates the YAP/TEAD4 transcription complex through its interacting proteins, such as transcription termination factor 2 (TTF2). These discoveries reveal a novel YAP/TEAD regulatory mechanism orchestrated by TEAD4, which provides molecular insights of Hippo-YAP regulation after SARS-CoV-2 infection.","journal":null,"year":2024,"id":502344,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1088565,"name":"Jong Hwan Kim","orcid":"0000-0001-6201-9602","position":1,"is_corresponding":false},{"id":1161594,"name":"Chang-Ru Tsai","orcid":"0000-0001-5672-1235","position":2,"is_corresponding":false},{"id":1352275,"name":"Jeffrey D Steimle","orcid":null,"position":3,"is_corresponding":false},{"id":6308,"name":"Jun Wang","orcid":"0000-0003-2509-9599","position":4,"is_corresponding":false},{"id":155287,"name":"Yufeng Shi","orcid":null,"position":5,"is_corresponding":false},{"id":1337585,"name":"Rich G Li","orcid":null,"position":6,"is_corresponding":false},{"id":577737,"name":"Bing Xie","orcid":"0000-0002-5409-4378","position":7,"is_corresponding":false},{"id":864507,"name":"Vaibhav Deshmukh","orcid":"0000-0002-0087-7545","position":8,"is_corresponding":false},{"id":373889,"name":"Shijie Liu","orcid":"0000-0002-2597-5416","position":9,"is_corresponding":false},{"id":108968,"name":"Xiao Li","orcid":"0000-0001-9785-4907","position":10,"is_corresponding":false},{"id":1352276,"name":"James F Martin","orcid":null,"position":11,"is_corresponding":false},{"id":666608,"name":"Fansen Meng","orcid":"0000-0003-3173-5512","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:10:23.709105Z","pmid":null,"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":[]}