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FMRP phosphorylation modulates neuronal translation through YTHDF1

文献类型：期刊论文

作者Zou, Zhongyu9,10; Wei, Jiangbo9,10; Chen, Yantao8; Kang, Yunhee7; Shi, Hailing9,10; Yang, Fan9,10; Shi, Zhuoyue6; Chen, Shijie5,8; Zhou, Ying7; Sepich-Poore, Caraline4,9
刊名MOLECULAR CELL
出版日期2023-12-07
卷号83期号:23
DOI10.1016/j.molcel.2023.10.028
文献子类Article
英文摘要RNA-binding proteins (RBPs) control messenger RNA fate in neurons. Here, we report a mechanism that the stimuli-induced neuronal translation is mediated by phosphorylation of a YTHDF1-binding protein FMRP. Mechanistically, YTHDF1 can condense with ribosomal proteins to promote the translation of its mRNA tar-gets. FMRP regulates this process by sequestering YTHDF1 away from the ribosome; upon neuronal stimu-lation, FMRP becomes phosphorylated and releases YTHDF1 for translation upregulation. We show that a new small molecule inhibitor of YTHDF1 can reverse fragile X syndrome (FXS) developmental defects associated with FMRP deficiency in an organoid model. Our study thus reveals that FMRP and its phosphorylation are important regulators of activity-dependent translation during neuronal development and stimulation and identifies YTHDF1 as a potential therapeutic target for FXS in which developmental defects caused by FMRP depletion could be reversed through YTHDF1 inhibition.
WOS关键词FRAGILE-X-SYNDROME ; MESSENGER-RNA TRANSLATION ; LOCAL PROTEIN-SYNTHESIS ; MEMORY ; ORGANOIDS ; BINDING ; KINASE
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
WOS记录号WOS:001135147200001
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/309635]  
专题新药研究国家重点实验室
通讯作者Jin, Peng; Luo, Cheng; He, Chuan
作者单位1.Zhejiang Chinese Med Univ, Sch Pharmaceut Sci, Hangzhou 310053, Peoples R China
2.Univ Texas Southwestern Med Ctr, Dept Biochem, 5323 Harry Hines Blvd, Dallas, TX 75390 USA;
3.Univ Chicago, Dept Neurobiol, Chicago, IL 60637 USA;
4.Univ Chicago, Dept Biochem & Mol Biol, Med Scientist Training Program, Chicago, IL 60637 USA;
5.UCAS, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou 310024, Peoples R China;
6.Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA;
7.Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Dept Cell Biol, Atlanta, GA 30322 USA;
8.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Chem Biol, Drug Discovery & Design Ctr,State Key Lab Drug Res, Shanghai 201203, Peoples R China;
9.Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA;
10.Univ Chicago, Dept Chem, Chicago, IL 60637 USA;
推荐引用方式
GB/T 7714		 Zou, Zhongyu,Wei, Jiangbo,Chen, Yantao,et al. FMRP phosphorylation modulates neuronal translation through YTHDF1[J]. MOLECULAR CELL,2023,83(23).
APA Zou, Zhongyu.,Wei, Jiangbo.,Chen, Yantao.,Kang, Yunhee.,Shi, Hailing.,...&He, Chuan.(2023).FMRP phosphorylation modulates neuronal translation through YTHDF1.MOLECULAR CELL,83(23).
MLA Zou, Zhongyu,et al."FMRP phosphorylation modulates neuronal translation through YTHDF1".MOLECULAR CELL 83.23(2023).

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来源：上海药物研究所

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