{"doi":"10.1101/2023.11.30.569413","title":"SARS-CoV-2 NSP13 interacts with TEAD to suppress Hippo-YAP signaling","abstract":"Abstract The Hippo pathway controls organ development, homeostasis, and regeneration primarily by modulating 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 induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) and SARS-CoV-2-infected human lung samples, 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, inhibits YAP transcriptional activity independent of the upstream Hippo kinases LATS1/2. Consistently, introducing NSP13 into cardiomyocytes suppresses an active form of YAP (YAP5SA) in vivo . Subsequent investigations on NSP13 mutants revealed that NSP13 helicase activity, including DNA binding and unwinding, is crucial for suppressing YAP transactivation. Mechanistically, TEAD4 serves as a platform to recruit NSP13 and YAP. NSP13 likely inactivates the YAP/TEAD4 transcription complex by remodeling chromatin to recruit proteins, such as transcription termination factor 2 (TTF2), to bind the YAP/TEAD/NSP13 complex. These findings reveal a novel YAP/TEAD regulatory mechanism and uncover molecular insights into Hippo-YAP regulation after SARS-CoV-2 infection.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":401765,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":31940,"name":"Jong-Hwan Kim","orcid":"0000-0002-9520-0771","position":1,"is_corresponding":false},{"id":1161594,"name":"Chang-Ru Tsai","orcid":"0000-0001-5672-1235","position":2,"is_corresponding":false},{"id":469568,"name":"Jeffrey D. Steimle","orcid":"0000-0002-1369-9661","position":3,"is_corresponding":false},{"id":1096654,"name":"Jun Wang","orcid":"0000-0002-7437-8503","position":4,"is_corresponding":false},{"id":1178714,"name":"Yufeng Shi","orcid":"0000-0001-8007-0479","position":5,"is_corresponding":false},{"id":628393,"name":"Gang Li","orcid":"0000-0001-9661-8304","position":6,"is_corresponding":false},{"id":666609,"name":"Bing Xie","orcid":"0000-0002-7408-6762","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":318079,"name":"Xiao Li","orcid":"0000-0001-8527-4438","position":10,"is_corresponding":false},{"id":295762,"name":"James F. Martin","orcid":"0000-0002-7842-9857","position":11,"is_corresponding":false},{"id":666608,"name":"Fansen Meng","orcid":"0000-0003-3173-5512","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T01:20:12.316631Z","pmid":"40667266","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":[]}