Language
English
Publication Date
9-23-2025
Journal
Elife
DOI
10.7554/eLife.100248
PMID
40985618
PMCID
PMC12456957
PubMedCentral® Posted Date
September 2025
PubMedCentral® Full Text Version
Post-print
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 human-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 mouse 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 in HEK293T cells. 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 in humans.
Keywords
Humans, Transcription Factors, Mice, Animals, Hippo Signaling Pathway, Signal Transduction, Protein Serine-Threonine Kinases, SARS-CoV-2, HEK293 Cells, YAP-Signaling Proteins, Viral Nonstructural Proteins, DNA-Binding Proteins, TEA Domain Transcription Factors, COVID-19, Adaptor Proteins, Signal Transducing, Myocytes, Cardiac, Muscle Proteins, Cell Cycle Proteins, Induced Pluripotent Stem Cells, RNA Helicases, Methyltransferases, Hela, Hippo pathway, NSP13, SARS-CoV2, TEAD, YAP, cardiomyocytes, cell biology, mouse, viruses
Published Open-Access
no
Recommended Citation
Meng, Fansen; Kim, Jong Hwan; Tsai, Chang-Ru; et al., "SARS-CoV-2 NSP13 Interacts With Tead To Suppress Hippo-Yap Signaling" (2025). Faculty and Staff Publications. 4000.
https://digitalcommons.library.tmc.edu/baylor_docs/4000
Included in
Clinical Epidemiology Commons, COVID-19 Commons, Medical Sciences Commons, Medical Specialties Commons