RNA甲基化
N6-甲基腺苷
脱甲基酶
基因敲除
甲基化
海马结构
海马体
基因剔除小鼠
生物
核糖核酸
信使核糖核酸
表型
内分泌学
内科学
医学
表观遗传学
基因
遗传学
受体
甲基转移酶
作者
Shu Liu,Jianbo Xiu,Caiyun Zhu,Kexin Meng,Chen Li,Rongrong Han,Tingfu Du,Lanlan Li,Lingdan Xu,Renjie Liu,Wanwan Zhu,Yan Shen,Qi Xu
标识
DOI:10.1038/s41467-021-27044-7
摘要
Abstract Post-transcriptional modifications of RNA, such as RNA methylation, can epigenetically regulate behavior, for instance learning and memory. However, it is unclear whether RNA methylation plays a critical role in the pathophysiology of major depression disorder (MDD). Here, we report that expression of the fat mass and obesity associated gene (FTO), an RNA demethylase, is downregulated in the hippocampus of patients with MDD and mouse models of depression. Suppressing Fto expression in the mouse hippocampus results in depression-like behaviors in adult mice, whereas overexpression of FTO expression leads to rescue of the depression-like phenotype. Epitranscriptomic profiling of N6-methyladenosine (m 6 A) RNA methylation in the hippocampus of Fto knockdown (KD), Fto knockout (cKO), and FTO-overexpressing (OE) mice allows us to identify adrenoceptor beta 2 ( Adrb2 ) mRNA as a target of FTO. ADRB2 stimulation rescues the depression-like behaviors in mice and spine loss induced by hippocampal Fto deficiency, possibly via the modulation of hippocampal SIRT1 expression by c-MYC. Our findings suggest that FTO is a regulator of a mechanism underlying depression-like behavior in mice.
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