南方科技大学知识苑(SUSTech KC): Arhgef2 regulates neural differentiation in the cerebral cortex through mRNA m6A-methylation of Npdc1 and Cend1

题名	Arhgef2 regulates neural differentiation in the cerebral cortex through mRNA m6A-methylation of Npdc1 and Cend1
作者	Zhou，Pei 1; Qi，Yifei 2; Fang，Xiang 1; Yang，Miaomiao 1; Zheng，Shuxin 1; Liao，Caihua 1; Qin，Fengying 1; Liu，Lili 1; Li，Hong 1; Li，Yan 1; Ravindran，Ethiraj 3,4,5; Sun，Chuanbo 1; Wei，Xinshu 1,6; Wang，Wen7 ; Fang，Liang7 ; Han，Dingding 1; Peng，Changgeng 8; Chen，Wei7 ; Li，Na 1; Kaindl，Angela M.3,4,5; Hu,Hao 1,6,9,10
通讯作者	Qi，Yifei; Hu,Hao
共同第一作者	Qi，Yifei
发表日期	2021-06-25
DOI	10.1016/j.isci.2021.102645
发表期刊	iScience 影响因子和分区
EISSN	2589-0042
卷号	24 期号:6
摘要	N-methyladenosine (mA) is emerging as a vital factor regulating neural differentiation. Here, we report that deficiency of Arhgef2, a novel cause of a neurodevelopmental disorder we identified recently, impairs neurogenesis, neurite outgrowth, and synaptic formation by regulating mA methylation. Arhgef2 knockout decreases expression of Mettl14 and total mA level significantly in the cerebral cortex. mA sequencing reveals that loss of Arhgef2 reduces mA methylation of 1,622 mRNAs, including Npdc1 and Cend1, which are both strongly associated with cell cycle exit and terminal neural differentiation. Arhgef2 deficiency decreases mA methylations of the Npdc1 and Cend1 mRNAs via down-regulation of Mettl14, and thereby inhibits the translation of Npdc1 and nuclear export of Cend1 mRNAs. Overexpression of Mettl14, Npdc1, and Cend1 rescue the abnormal phenotypes in Arhgef2 knockout mice, respectively. Our study provides a critical insight into a mechanism by which defective Arhgef2 mediates mA-tagged target mRNAs to impair neural differentiation.
关键词	Cellular Neuroscience Developmental Neuroscience Molecular Neuroscience
相关链接	[Scopus记录]
收录类别	SCI
语种	英语
学校署名	其他
WOS记录号	WOS:000667301700074
Scopus记录号	2-s2.0-85108139669
来源库	Scopus
引用统计	被引频次[WOS]：7
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/230170
专题	前沿与交叉科学研究院生命科学学院
作者单位	1.Laboratory of Medical Systems Biology,Guangzhou Women and Children's Medical Center,Guangzhou Medical University,Guangzhou,510623,China 2.Division of Uterine Vascular Biology,Guangzhou Women and Children's Medical Center,Guangzhou Medical University,Guangzhou,510623,China 3.Charité - Universitätsmedizin Berlin,Institute of Cell Biology and Neurobiology,Berlin,Germany 4.Charité - Universitätsmedizin Berlin,Department of Pediatric Neurology,Berlin,Germany 5.Charité - Universitätsmedizin Berlin,Center for Chronically Sick Children,Berlin,Germany 6.School of Medicine,South China University of Technology,Guangzhou,510006,China 7.Shenzhen Key Laboratory of Gene Regulation and Systems Biology,School of Life Sciences and Academy for Advanced Interdisciplinary Studies,Southern University of Science and Technology,Shenzhen,518005,China 8.The First Rehabilitation Hospital of Shanghai,Tongji University School of Medicine,Shanghai,200029,China 9.Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease,Guangzhou Women and Children's Medical Center,Guangzhou Medical University,Guangzhou,510623,China 10.Third Affiliated Hospital of Zhengzhou University,Zhengzhou,450052,China
推荐引用方式 GB/T 7714	Zhou，Pei,Qi，Yifei,Fang，Xiang,et al. Arhgef2 regulates neural differentiation in the cerebral cortex through mRNA m6A-methylation of Npdc1 and Cend1[J]. iScience,2021,24(6).
APA	Zhou，Pei.,Qi，Yifei.,Fang，Xiang.,Yang，Miaomiao.,Zheng，Shuxin.,...&Hu,Hao.(2021).Arhgef2 regulates neural differentiation in the cerebral cortex through mRNA m6A-methylation of Npdc1 and Cend1.iScience,24(6).
MLA	Zhou，Pei,et al."Arhgef2 regulates neural differentiation in the cerebral cortex through mRNA m6A-methylation of Npdc1 and Cend1".iScience 24.6(2021).