首页|Engagement of N6-methyladenisine methylation of Gng4 mRNA in astrocyte dysfunction regulated by CircHECW2

Engagement of N6-methyladenisine methylation of Gng4 mRNA in astrocyte dysfunction regulated by CircHECW2

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The N6-methyladenosine(m6A)modification is the most prevalent modification of eukaryotic mRNAs and plays a crucial role in various physiological processes by regulating the stability or function of target mRNAs.Accumulating evidence has suggested that m6A methylation may be involved in the pathological process of major depressive disorder(MDD),a common neuropsychiatric disorder with an unclear aetiology.Here,we found that the levels of the circular RNA HECW2(circHECW2)were significantly increased in the plasma of both MDD patients and the chronic unpredictable stress(CUS)mouse model.Notably,the downregulation of circHECW2 attenuated astrocyte dysfunction and depression-like behaviors induced by CUS.Furthermore,we demonstrated that the downregulation of cir-cHECW2 increased the expression of the methylase WTAP,leading to an increase in Gng4 expression via m6A modifications.Our findings provide functional insight into the correlation between circHECW2 and m6A methylation,suggesting that circHECW2 may represent a potential target for MDD treatment.

N6-MethyladenosineDepressioncircHECW2AstrocyteWTAPUbiquitinationGNG4Dysfunction

Ying Bai、Di Chang、Hui Ren、Minzi Ju、Yu Wang、Biling Chen、Han Li、Xue Liu、Daxing Li、Xinchen Huo、Xiaofei Guo、Mengze Tong、Ying Tan、Honghong Yao、Bing Han

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Department of Pharmacology,Jiangsu Provincial Key Laboratory of Critical Care Medicine,School of Medicine,Southeast University,Nanjing 210009,China

Department of Radiology,Zhongda Hospital,Jiangsu Key Laboratory of Molecular and Functional Imaging,Medical School of Southeast University,Nanjing 210009,China

Co-Innovation Center of Neuroregeneration,Nantong University,Nantong 226001,China

Institute of Life Sciences,Key Laboratory of Developmental Genes and Human Disease,Southeast University,Nanjing 210096,China

Center for Global Health,School of Public Health,Nanjing Medical University,Nanjing 211166,China

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Science and Technology Innovation 2030-Major Project of the Ministry of Science and Technology of ChinaNational Science Fund Distinguished Young Scholars,China国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金江苏省自然科学基金ZhiShan Scholar Program of Southeast University,ChinaZhiShan Scholar Program of Southeast University,ChinaJiangsu Provincial Key Laboratory of Critical Care Medicine,ChinaOpen Project Program of the Key Laboratory of Developmental Genes and Human Diseases of the Ministry of Education,China

2021ZD0202904/2021ZD0202900820250338223011582273914819035918237202482003733BK202003582242022R400592242021R40023JSKLCCM-2022-02-008LDGHD202304

2024

药学学报(英文版)

药学学报(英文版)

CSTPCD
ISSN:
年,卷(期):2024.14(4)
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