Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Artículo científico |
| Language: | en |
| Published: |
Molecular cell
2025
|
| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40267921/ |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1868266214104498176 |
|---|---|
| author | He, Jianfeng Zhu, Yongyi Tian, Zichao Liu, Mengqin Gao, Anmin Fu, Wangmi Lu, Fei Sun, Yutong Guo, Yajun Pan, Rongqing Ji, Yuchen Chen, Jianxiang Lu, Huasong Lin, Juan Liang, Xingguo Kim, Chun Zhou, Chun Jiao, Huipeng |
| author_facet | He, Jianfeng Zhu, Yongyi Tian, Zichao Liu, Mengqin Gao, Anmin Fu, Wangmi Lu, Fei Sun, Yutong Guo, Yajun Pan, Rongqing Ji, Yuchen Chen, Jianxiang Lu, Huasong Lin, Juan Liang, Xingguo Kim, Chun Zhou, Chun Jiao, Huipeng He, Jianfeng Zhu, Yongyi Tian, Zichao Liu, Mengqin Gao, Anmin Fu, Wangmi Lu, Fei Sun, Yutong Guo, Yajun Pan, Rongqing Ji, Yuchen Chen, Jianxiang Lu, Huasong Lin, Juan Liang, Xingguo Kim, Chun Zhou, Chun Jiao, Huipeng |
| collection | PubMed - marine biology |
| contents | ZBP1 senses spliceosome stress through Z-RNA:DNA hybrid recognition. He, Jianfeng Zhu, Yongyi Tian, Zichao Liu, Mengqin Gao, Anmin Fu, Wangmi Lu, Fei Sun, Yutong Guo, Yajun Pan, Rongqing Ji, Yuchen Chen, Jianxiang Lu, Huasong Lin, Juan Liang, Xingguo Kim, Chun Zhou, Chun Jiao, Huipeng Animals Humans Mice Apoptosis DNA, Z-Form DNA-Binding Proteins HEK293 Cells HeLa Cells Models, Molecular Nucleic Acid Conformation Protein Binding RNA, Z-Form RNA-Binding Proteins Signal Transduction Spliceosomes Z-DNA-binding protein 1 (ZBP1; also known as DAI or DLM-1) regulates cell death and inflammation by sensing left-handed double-helical nucleic acids, including Z-RNA and Z-DNA. However, the physiological conditions that generate Z-form nucleic acids (Z-NAs) and activate ZBP1-dependent signaling pathways remain largely elusive. In this study, we developed a probe, Zα-mFc, that specifically detected both Z-DNA and Z-RNA. Utilizing this probe, we discovered that inhibiting spliceosome causes nuclear accumulation of Z-RNA:DNA hybrids, which are sensed by ZBP1 via its Zα domains, triggering apoptosis and necroptosis in mammalian cells. Furthermore, we solved crystal structures of the human or mouse Zα1 domain complexed with a 6-bp RNA:DNA hybrid, revealing that the RNA:DNA hybrid adopts a left-handed conformation. Our findings demonstrate that the spliceosome acts as a checkpoint preventing accumulation of Z-RNA:DNA hybrids, which potentially function as endogenous ligands activating ZBP1-dependent cell death pathways. |
| format | Artículo científico |
| id | pubmed_40267921 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Molecular cell |
| record_format | pubmed |
| spellingShingle | ZBP1 senses spliceosome stress through Z-RNA:DNA hybrid recognition. He, Jianfeng Zhu, Yongyi Tian, Zichao Liu, Mengqin Gao, Anmin Fu, Wangmi Lu, Fei Sun, Yutong Guo, Yajun Pan, Rongqing Ji, Yuchen Chen, Jianxiang Lu, Huasong Lin, Juan Liang, Xingguo Kim, Chun Zhou, Chun Jiao, Huipeng Animals Humans Mice Apoptosis DNA, Z-Form DNA-Binding Proteins HEK293 Cells HeLa Cells Models, Molecular Nucleic Acid Conformation Protein Binding RNA, Z-Form RNA-Binding Proteins Signal Transduction Spliceosomes ZBP1 senses spliceosome stress through Z-RNA:DNA hybrid recognition. He, Jianfeng Zhu, Yongyi Tian, Zichao Liu, Mengqin Gao, Anmin Fu, Wangmi Lu, Fei Sun, Yutong Guo, Yajun Pan, Rongqing Ji, Yuchen Chen, Jianxiang Lu, Huasong Lin, Juan Liang, Xingguo Kim, Chun Zhou, Chun Jiao, Huipeng Animals Humans Mice Apoptosis DNA, Z-Form DNA-Binding Proteins HEK293 Cells HeLa Cells Models, Molecular Nucleic Acid Conformation Protein Binding RNA, Z-Form RNA-Binding Proteins Signal Transduction Spliceosomes Z-DNA-binding protein 1 (ZBP1; also known as DAI or DLM-1) regulates cell death and inflammation by sensing left-handed double-helical nucleic acids, including Z-RNA and Z-DNA. However, the physiological conditions that generate Z-form nucleic acids (Z-NAs) and activate ZBP1-dependent signaling pathways remain largely elusive. In this study, we developed a probe, Zα-mFc, that specifically detected both Z-DNA and Z-RNA. Utilizing this probe, we discovered that inhibiting spliceosome causes nuclear accumulation of Z-RNA:DNA hybrids, which are sensed by ZBP1 via its Zα domains, triggering apoptosis and necroptosis in mammalian cells. Furthermore, we solved crystal structures of the human or mouse Zα1 domain complexed with a 6-bp RNA:DNA hybrid, revealing that the RNA:DNA hybrid adopts a left-handed conformation. Our findings demonstrate that the spliceosome acts as a checkpoint preventing accumulation of Z-RNA:DNA hybrids, which potentially function as endogenous ligands activating ZBP1-dependent cell death pathways. |
| title | ZBP1 senses spliceosome stress through Z-RNA:DNA hybrid recognition. |
| topic | Animals Humans Mice Apoptosis DNA, Z-Form DNA-Binding Proteins HEK293 Cells HeLa Cells Models, Molecular Nucleic Acid Conformation Protein Binding RNA, Z-Form RNA-Binding Proteins Signal Transduction Spliceosomes |
| url | https://pubmed.ncbi.nlm.nih.gov/40267921/ |