Mettl3-m⁶A-NPY axis governing neuron-microglia interaction regulates sleep amount of mice.

IF 13 1区生物学 Q1 CELL BIOLOGY

Cell Discovery Pub Date : 2025-02-04 DOI:10.1038/s41421-024-00756-y

Qihang Sun, Jinpiao Zhu, Xingsen Zhao, Xiaoli Huang, Wenzheng Qu, Xia Tang, Daqing Ma, Qiang Shu, Xuekun Li

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引用次数: 0

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.

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Mettl3-m6A-NPY轴调节神经元与小胶质细胞之间的相互作用，从而调节小鼠的睡眠量。

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来源期刊

Cell Discovery Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

24.20

自引率

0.60%

发文量

120

审稿时长

20 weeks

期刊介绍： Cell Discovery is a cutting-edge, open access journal published by Springer Nature in collaboration with the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CAS). Our aim is to provide a dynamic and accessible platform for scientists to showcase their exceptional original research. Cell Discovery covers a wide range of topics within the fields of molecular and cell biology. We eagerly publish results of great significance and that are of broad interest to the scientific community. With an international authorship and a focus on basic life sciences, our journal is a valued member of Springer Nature's prestigious Molecular Cell Biology journals. In summary, Cell Discovery offers a fresh approach to scholarly publishing, enabling scientists from around the world to share their exceptional findings in molecular and cell biology.