Z-nucleic acid-mediated PANoptosis in infection, inflammation, and cancer
6 affiliations
- 1Department of Biomedicine and Translational Research, Research Institute for Bioscience and Biotechnology, Kathmandu, Nepal
- 2Department of Biotechnology, School of Science, Kathmandu University, Dhulikhel, Nepal
- 3Department of Biological Sciences, College of Natural Science, Seoul National University, Seoul, South Korea
- 4Department of Biological Sciences, College of Natural Science, Seoul National University, Seoul, South Korea. [email protected]
- 5Nexus Institute of Research and Innovation (NIRI), Kathmandu, Nepal. [email protected]
- 6The Institute of Molecular Biology and Genetics (IMBG), Seoul National University, Seoul, South Korea. [email protected]
Abstract
Nucleic acids serve not only as carriers of genetic information but also as potent immunological signals that shape innate and adaptive immune responses. Their immunogenicity is determined by their origin, subcellular localization, structural conformation, and the host sensors that detect them. Within this landscape, Z-nucleic acids, including Z-RNA and Z-DNA, have emerged from biological noise to key regulators of immune activation, particularly through their ability to induce inflammatory cell death pathways. Both host and pathogens can generate Z-nucleic acids, yet the mechanisms governing their formation and regulation remain incompletely understood. In mammals, ZBP1 and ADAR1 are the only known Z-nucleic acid sensors, while some pathogens encode Z-binding proteins to evade detection. Although critical for host defense, dysregulated Z-nucleic acid signaling can drive autoimmunity and chronic inflammation. This review synthesizes current structural and functional principles of Z-nucleic acid recognition and highlights emerging therapeutic opportunities across infectious diseases, inflammatory disorders, and cancer. This review summarizes the mechanisms underlying the generation and regulation of Z-nucleic acids and discusses their sensing by ADAR1 and ZBP1 in cell death and inflammatory signalling, with broad implications for infection, inflammation, and cancer.
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BibTeX
@article{thapa2026znucleic,
title = {{Z-nucleic acid-mediated PANoptosis in infection, inflammation, and cancer}},
author = {Nisha Thapa and Aro Kim and Paritosh Patel and Minh Quan Nguyen and Ein Lee and Rajendra Karki},
journal = {Communications Biology},
year = {2026},
month = may,
doi = {10.1038/s42003-026-10368-9},
url = {https://doi.org/10.1038/s42003-026-10368-9},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Z-nucleic acid-mediated PANoptosis in infection, inflammation, and cancer
AU - Nisha Thapa
AU - Aro Kim
AU - Paritosh Patel
AU - Minh Quan Nguyen
AU - Ein Lee
AU - Rajendra Karki
PY - 2026
DA - 2026/05/27
JO - Communications Biology
DO - 10.1038/s42003-026-10368-9
UR - https://doi.org/10.1038/s42003-026-10368-9
AB - Nucleic acids serve not only as carriers of genetic information but also as potent immunological signals that shape innate and adaptive immune responses. Their immunogenicity is determined by their origin, subcellular localization, structural conformation, and the host sensors that detect them. Within this landscape, Z-nucleic acids, including Z-RNA and Z-DNA, have emerged from biological noise to key regulators of immune activation, particularly through their ability to induce inflammatory cell death pathways. Both host and pathogens can generate Z-nucleic acids, yet the mechanisms governing their formation and regulation remain incompletely understood. In mammals, ZBP1 and ADAR1 are the only known Z-nucleic acid sensors, while some pathogens encode Z-binding proteins to evade detection. Although critical for host defense, dysregulated Z-nucleic acid signaling can drive autoimmunity and chronic inflammation. This review synthesizes current structural and functional principles of Z-nucleic acid recognition and highlights emerging therapeutic opportunities across infectious diseases, inflammatory disorders, and cancer. This review summarizes the mechanisms underlying the generation and regulation of Z-nucleic acids and discusses their sensing by ADAR1 and ZBP1 in cell death and inflammatory signalling, with broad implications for infection, inflammation, and cancer.
SN - 2399-3642
ER -