Mammalian <scp>TatD DNase</scp> domain containing 1 ( <i>TATDN1</i> ) is a proteostasis‐responsive gene with roles in ventricular structure and neuromuscular function
The characterization of highly conserved but poorly understood genes often reveals unexpected biological roles, advancing our understanding of disease mechanisms. One such gene is Mammalian TatD DNase domain containing 1 (Tatdn1), the mammalian homolog of bacterial Twin-arginine translocation D (TatD), a protein proposed to have roles either in DNA degradation or protein quality control in unicellular organisms. Despite its association with different pathologies, including several cancer types and cardiovascular diseases, the role of TATDN1 in mammals remains unexplored. Here, we demonstrate that Tatdn1 encodes a cytoplasmic protein that does not participate in DNA degradation but is upregulated in cells under proteostasis stress. Tatdn1-deficient mice exhibit dysregulated expression of genes involved in membrane and extracellular protein biology, along with mild dilated cardiomyopathy and impaired motor coordination. These findings identify TATDN1 as a key player in cytosolic processes linked to protein homeostasis, with significant physiological implications for cardiac and neurological function.
Authors
- Albert Giralt (ORCID: https://orcid.org/0000-0001-5334-0963)
- Juan García Valero (ORCID: https://orcid.org/0000-0003-3193-9099)
- Javier Inserte (ORCID: https://orcid.org/0000-0002-4736-5010)
- Sara Borràs‐Pernas
- Francesc Tebar (ORCID: https://orcid.org/0000-0002-9522-9726)
- Marta Llovera (ORCID: https://orcid.org/0000-0001-8399-6867)
- Anna Sancho‐Balsells (ORCID: https://orcid.org/0000-0003-2053-7211)
- Sara Hernández (ORCID: https://orcid.org/0000-0002-6451-724X)
- Daniel Sanchı́s (ORCID: https://orcid.org/0000-0003-0047-8533)
- Jesper Velgaard Olsen (ORCID: https://orcid.org/0000-0002-4747-4938)
- Elisabet Miró‐Casas (ORCID: https://orcid.org/0000-0002-2058-5961)
- Marisol Ruiz‐Meana (ORCID: https://orcid.org/0000-0002-4067-4638)
- Aida Beà (ORCID: https://orcid.org/0000-0002-9733-4618)
- Xavier Cañas
- Gisel Barés
- David Aluja (ORCID: https://orcid.org/0000-0002-0448-9419)
- Joan X. Comella (ORCID: https://orcid.org/0000-0002-6218-0786)
- Ana Martínez‐Val (ORCID: https://orcid.org/0000-0002-8784-3822)
- Patricia Pérez‐Galán (ORCID: https://orcid.org/0000-0003-3895-5024)
- Sandra García‐Carpi
Institutions
- Universitat Autònoma de Barcelona (ES)
- University of Copenhagen (DK)
- Universitat de Lleida (ES)
- Novo Nordisk Foundation (DK)
- Instituto de Salud Carlos III (ES)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Centro de Investigación en Red en Enfermedades Cardiovasculares (ES)
- Departament de Salut (ES)
- Vall d'Hebron Institut de Recerca (ES)
- Vall d'Hebron Hospital Universitari (ES)
- Instituto de Investigación Biomédica de Lleida (ES)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- FEBS Journal
- Published
- 2025-03-23
- DOI
- https://doi.org/10.1111/febs.70077
- Primary Topic
- RNA and protein synthesis mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Fundació la Marató de TV3
- Ministerio de Ciencia, Innovación y Universidades
- Generalitat de Catalunya
- Universitat de Lleida
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Instituto de Salud Carlos III
- H2020 European Research Council