Mettl3-m6A-NPY axis governing neuron–microglia interaction regulates sleep amount of mice
Abstract Sleep behavior is regulated by diverse mechanisms including genetics, neuromodulation and environmental signals. However, it remains completely unknown regarding the roles of epitranscriptomics in regulating sleep behavior. In the present study, we showed that the deficiency of RNA m6A meth...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-02-01
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| Series: | Cell Discovery |
| Online Access: | https://doi.org/10.1038/s41421-024-00756-y |
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| author | Qihang Sun Jinpiao Zhu Xingsen Zhao Xiaoli Huang Wenzheng Qu Xia Tang Daqing Ma Qiang Shu Xuekun Li |
| author_facet | Qihang Sun Jinpiao Zhu Xingsen Zhao Xiaoli Huang Wenzheng Qu Xia Tang Daqing Ma Qiang Shu Xuekun Li |
| author_sort | Qihang Sun |
| collection | DOAJ |
| description | Abstract Sleep behavior is regulated by diverse mechanisms including genetics, neuromodulation and environmental signals. However, it remains completely unknown regarding the roles of epitranscriptomics in regulating sleep behavior. In the present study, we showed that the deficiency of RNA m6A methyltransferase Mettl3 in excitatory neurons specifically induces microglia activation, neuroinflammation and neuronal loss in thalamus of mice. Mettl3 deficiency remarkably disrupts sleep rhythm and reduces the amount of non-rapid eye movement sleep. We also showed that Mettl3 regulates neuropeptide Y (NPY) via m6A modification and Mettl3 conditional knockout (cKO) mice displayed significantly decreased expression of NPY in thalamus. In addition, the dynamic distribution pattern of NPY is observed during wake-sleep cycle in cKO mice. Ectopic expression of Mettl3 and NPY significantly inhibits microglia activation and neuronal loss in thalamus, and restores the disrupted sleep behavior of cKO mice. Collectively, our study has revealed the critical function of Mettl3-m6A-NPY axis in regulating sleep behavior. |
| format | Article |
| id | doaj-art-de60c7545fe343eeba60dd4aebf06e01 |
| institution | Kabale University |
| issn | 2056-5968 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Discovery |
| spelling | doaj-art-de60c7545fe343eeba60dd4aebf06e012025-02-09T12:11:53ZengNature Publishing GroupCell Discovery2056-59682025-02-0111111810.1038/s41421-024-00756-yMettl3-m6A-NPY axis governing neuron–microglia interaction regulates sleep amount of miceQihang Sun0Jinpiao Zhu1Xingsen Zhao2Xiaoli Huang3Wenzheng Qu4Xia Tang5Daqing Ma6Qiang Shu7Xuekun Li8Children’s Hospital, School of Medicine, Zhejiang University, National Clinical Research Center for Child HealthChildren’s Hospital, School of Medicine, Zhejiang University, National Clinical Research Center for Child HealthInstitute of Biotechnology, Xianghu LaboratoryChildren’s Hospital, School of Medicine, Zhejiang University, National Clinical Research Center for Child HealthChildren’s Hospital, School of Medicine, Zhejiang University, National Clinical Research Center for Child HealthChildren’s Hospital, School of Medicine, Zhejiang University, National Clinical Research Center for Child HealthDepartment of Rehabilitation, Perioperative and Systems Medicine Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child HealthChildren’s Hospital, School of Medicine, Zhejiang University, National Clinical Research Center for Child HealthChildren’s Hospital, School of Medicine, Zhejiang University, National Clinical Research Center for Child HealthAbstract Sleep behavior is regulated by diverse mechanisms including genetics, neuromodulation and environmental signals. However, it remains completely unknown regarding the roles of epitranscriptomics in regulating sleep behavior. In the present study, we showed that the deficiency of RNA m6A methyltransferase Mettl3 in excitatory neurons specifically induces microglia activation, neuroinflammation and neuronal loss in thalamus of mice. Mettl3 deficiency remarkably disrupts sleep rhythm and reduces the amount of non-rapid eye movement sleep. We also showed that Mettl3 regulates neuropeptide Y (NPY) via m6A modification and Mettl3 conditional knockout (cKO) mice displayed significantly decreased expression of NPY in thalamus. In addition, the dynamic distribution pattern of NPY is observed during wake-sleep cycle in cKO mice. Ectopic expression of Mettl3 and NPY significantly inhibits microglia activation and neuronal loss in thalamus, and restores the disrupted sleep behavior of cKO mice. Collectively, our study has revealed the critical function of Mettl3-m6A-NPY axis in regulating sleep behavior.https://doi.org/10.1038/s41421-024-00756-y |
| spellingShingle | Qihang Sun Jinpiao Zhu Xingsen Zhao Xiaoli Huang Wenzheng Qu Xia Tang Daqing Ma Qiang Shu Xuekun Li Mettl3-m6A-NPY axis governing neuron–microglia interaction regulates sleep amount of mice Cell Discovery |
| title | Mettl3-m6A-NPY axis governing neuron–microglia interaction regulates sleep amount of mice |
| title_full | Mettl3-m6A-NPY axis governing neuron–microglia interaction regulates sleep amount of mice |
| title_fullStr | Mettl3-m6A-NPY axis governing neuron–microglia interaction regulates sleep amount of mice |
| title_full_unstemmed | Mettl3-m6A-NPY axis governing neuron–microglia interaction regulates sleep amount of mice |
| title_short | Mettl3-m6A-NPY axis governing neuron–microglia interaction regulates sleep amount of mice |
| title_sort | mettl3 m6a npy axis governing neuron microglia interaction regulates sleep amount of mice |
| url | https://doi.org/10.1038/s41421-024-00756-y |
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