NLRP7 maintains the genomic stability during early human embryogenesis via mediating alternative splicing
Abstract Genomic instability is the main cause of abnormal embryo development and abortion. NLRP7 dysfunctions affect embryonic development and lead to Hydatidiform Moles, but the underlying mechanisms remain largely elusive. Here, we show that NLRP7 knockout affects the genetic stability, resulting...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07571-5 |
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| author | Zhongliang Chen Liangxia Jiang Min Su Qibing Zeng Peng Luo Liangzhao Chu |
| author_facet | Zhongliang Chen Liangxia Jiang Min Su Qibing Zeng Peng Luo Liangzhao Chu |
| author_sort | Zhongliang Chen |
| collection | DOAJ |
| description | Abstract Genomic instability is the main cause of abnormal embryo development and abortion. NLRP7 dysfunctions affect embryonic development and lead to Hydatidiform Moles, but the underlying mechanisms remain largely elusive. Here, we show that NLRP7 knockout affects the genetic stability, resulting in increased DNA damage in both human embryonic stem cells and blastoids, making embryonic cells in blastoids more susceptible to apoptosis. Mechanistically, NLRP7 can interact with factors related to alternative splicing and DNA damage response, including DDX39B, PRPF8, THRAP3 and PARP1. Moreover, NLRP7 dysfunction leads to abnormal alternative splicing of genes involved in homologous recombination in human embryonic stem cells, Such as Brca1 and Rad51. These results indicate that NLRP7-mediated Alternative splicing is potentially required for the maintenance of genome integrity during early human embryogenesis. Together, this study uncovers that NLRP7 plays an essential role in the maintenance of genetic stability during early human embryonic development by regulating alternative splicing of homologous recombination-related genes. |
| format | Article |
| id | doaj-art-98d47a08a46f4b848ede6f87419b9134 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-98d47a08a46f4b848ede6f87419b91342025-01-26T12:48:11ZengNature PortfolioCommunications Biology2399-36422025-01-018111310.1038/s42003-025-07571-5NLRP7 maintains the genomic stability during early human embryogenesis via mediating alternative splicingZhongliang Chen0Liangxia Jiang1Min Su2Qibing Zeng3Peng Luo4Liangzhao Chu5Department of Neurosurgery, The Affiliated Hospital of Guizhou Medical UniversityDepartment of Pathophysiology, School of Basic Medicine, Guizhou Medical UniversityGuizhou Province Key Laboratory of Regenerative Medicine, Guizhou Medical UniversityKey Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical UniversityKey Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical UniversityDepartment of Neurosurgery, The Affiliated Hospital of Guizhou Medical UniversityAbstract Genomic instability is the main cause of abnormal embryo development and abortion. NLRP7 dysfunctions affect embryonic development and lead to Hydatidiform Moles, but the underlying mechanisms remain largely elusive. Here, we show that NLRP7 knockout affects the genetic stability, resulting in increased DNA damage in both human embryonic stem cells and blastoids, making embryonic cells in blastoids more susceptible to apoptosis. Mechanistically, NLRP7 can interact with factors related to alternative splicing and DNA damage response, including DDX39B, PRPF8, THRAP3 and PARP1. Moreover, NLRP7 dysfunction leads to abnormal alternative splicing of genes involved in homologous recombination in human embryonic stem cells, Such as Brca1 and Rad51. These results indicate that NLRP7-mediated Alternative splicing is potentially required for the maintenance of genome integrity during early human embryogenesis. Together, this study uncovers that NLRP7 plays an essential role in the maintenance of genetic stability during early human embryonic development by regulating alternative splicing of homologous recombination-related genes.https://doi.org/10.1038/s42003-025-07571-5 |
| spellingShingle | Zhongliang Chen Liangxia Jiang Min Su Qibing Zeng Peng Luo Liangzhao Chu NLRP7 maintains the genomic stability during early human embryogenesis via mediating alternative splicing Communications Biology |
| title | NLRP7 maintains the genomic stability during early human embryogenesis via mediating alternative splicing |
| title_full | NLRP7 maintains the genomic stability during early human embryogenesis via mediating alternative splicing |
| title_fullStr | NLRP7 maintains the genomic stability during early human embryogenesis via mediating alternative splicing |
| title_full_unstemmed | NLRP7 maintains the genomic stability during early human embryogenesis via mediating alternative splicing |
| title_short | NLRP7 maintains the genomic stability during early human embryogenesis via mediating alternative splicing |
| title_sort | nlrp7 maintains the genomic stability during early human embryogenesis via mediating alternative splicing |
| url | https://doi.org/10.1038/s42003-025-07571-5 |
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