Rett syndrome linked to defects in forming the MeCP2/Rbfox/LASR complex in mouse models

doi:10.1038/s41467-021-26084-3

	Rett syndrome linked to defects in forming the MeCP2/Rbfox/LASR complex in mouse models
	Jiang, Yan 1; Fu, Xing 2; Zhang, Yuhan 3,4; Wang, Shen-Fei 1; Zhu, Hong 1; Wang, Wei-Kang 1; Zhang, Lin 5; Wu, Ping 6; Wong, Catherine C. L.6,9; Li, Jinsong 5; Ma, Jinbiao 3; Guan, Ji-Song7,8 ; Huang, Ying 4; Hui, Jingyi 1
	2021-10-01
发表期刊	NATURE COMMUNICATIONS (IF:14.7[JCR-2023],16.1[5-Year])
EISSN	2041-1723
卷号	12 期号:1
DOI	10.1038/s41467-021-26084-3
摘要	Rett syndrome (RTT) is a severe neurological disorder and a leading cause of intellectual disability in young females. RTT is mainly caused by mutations found in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2). Despite extensive studies, the molecular mechanism underlying RTT pathogenesis is still poorly understood. Here, we report MeCP2 as a key subunit of a higher-order multiunit protein complex Rbfox/LASR. Defective MeCP2 in RTT mouse models disrupts the assembly of the MeCP2/Rbfox/LASR complex, leading to reduced binding of Rbfox proteins to target pre-mRNAs and aberrant splicing of Nrxns and Nlgn1 critical for synaptic plasticity. We further show that MeCP2 disease mutants display defective condensate properties and fail to promote phase-separated condensates with Rbfox proteins in vitro and in cultured cells. These data link an impaired function of MeCP2 with disease mutation in splicing control to its defective properties in mediating the higher-order assembly of the MeCP2/Rbfox/LASR complex. MeCP2 mutations can cause Rett syndrome, a severe childhood neurological disorder. Here the authors show that MeCP2 mediates the higher-order assembly of a large splicing complex Rbfox/LASR, which is disrupted in the mouse models of Rett syndrome.
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收录类别	SCIE
语种	英语
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000702753200012
出版者	NATURE PORTFOLIO
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/128417
专题	生命科学与技术学院_PI研究组_管吉松组
通讯作者	Huang, Ying; Hui, Jingyi
作者单位	1.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Ctr Excellence Mol Cell Sci,State Key Lab Mol Bio, Shanghai 200031, Peoples R China; 2.Chinese Acad Sci, Shanghai Ctr Plant Stress Biol, Shanghai 201602, Peoples R China; 3.Fudan Univ, Collaborat Innovat Ctr Genet & Dev, Sch Life Sci,Dept Biochem, Inst Plant Biol,State Key Lab Genet Engn, Shanghai 200438, Peoples R China; 4.Shanghai Jiao Tong Univ, Xinhua Hosp, Shanghai Key Lab Biliary Tract Dis Res, Dept Gen Surg,State Key Lab Oncogenes & Related G, Shanghai 200092, Peoples R China; 5.Chinese Acad Sci, Univ Chinese Acad Sci, Ctr Excellence Mol Cell Sci,Shanghai Key Lab Mol, Shanghai Inst Biochem & Cell Biol,State Key Lab C, Shanghai 200031, Peoples R China; 6.Chinese Acad Sci, Shanghai Adv Res Inst, Zhangjiang Lab, Natl Facil Prot Sci Shanghai, Shanghai 201210, Peoples R China; 7.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China; 8.Chinese Acad Sci, Ctr Excellence Brain Sci & Intelligence Technol, Shanghai 200031, Peoples R China; 9.Peking Univ, Sch Basic Med Sci, Hlth Sci Ctr, Ctr Precis Med Multi Res, Beijing 100191, Peoples R China
推荐引用方式 GB/T 7714	Jiang, Yan,Fu, Xing,Zhang, Yuhan,et al. Rett syndrome linked to defects in forming the MeCP2/Rbfox/LASR complex in mouse models[J]. NATURE COMMUNICATIONS,2021,12(1).
APA	Jiang, Yan.,Fu, Xing.,Zhang, Yuhan.,Wang, Shen-Fei.,Zhu, Hong.,...&Hui, Jingyi.(2021).Rett syndrome linked to defects in forming the MeCP2/Rbfox/LASR complex in mouse models.NATURE COMMUNICATIONS,12(1).
MLA	Jiang, Yan,et al."Rett syndrome linked to defects in forming the MeCP2/Rbfox/LASR complex in mouse models".NATURE COMMUNICATIONS 12.1(2021).