下调和上调
RNA甲基化
N6-甲基腺苷
甲基化
海马体
脱甲基酶
内科学
信使核糖核酸
化学
内分泌学
调节器
生物
细胞生物学
甲基转移酶
医学
基因
生物化学
表观遗传学
作者
Yanqing Wang,Zimei Wu,Ying He,Xiaoying Zeng,Zijuan Gu,Xianxi Zhou,Wenwen Si,Dongfeng Chen
出处
期刊:Neuropeptides
[Elsevier]
日期:2024-06-01
卷期号:105: 102428-102428
标识
DOI:10.1016/j.npep.2024.102428
摘要
RNA methylation can epigenetically regulate learning and memory. However, it is unclear whether RNA methylation plays a critical role in the pathophysiology of Vascular dementia (VD). Here, we report that expression of the fat mass and obesity associated gene (FTO), an RNA demethylase, is downregulated in the hippocampus in models of VD. Through prediction and dual-luciferase reporters validation studies, we observed that miRNA-711 was upregulated after VD and could bind to the 3'-untranslated region of FTO mRNA and regulate its expression in vitro. Methylated RNA immunoprecipitation (MeRIP)-qPCR assay and functional study confirmed that Syn1 was an important target gene of FTO. This suggests that FTO is an important regulator of Syn1. FTO upregulation by inhibition of miR-711 in the hippocampus relieves synaptic association protein and synapse deterioration in vivo, whereas FTO downregulation by miR-711 agomir in the hippocampus leads to aggravate the synapse deterioration. FTO upregulation by inhibition of miR-711 relieves cognitive impairment of rats VD model, whereas FTO downregulation by miR-711 deteriorate cognitive impairment. Our findings suggest that FTO is a regulator of a mechanism underlying RNA methylation associated with spatial cognitive dysfunction after chronic cerebral hypoperfusion.
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