干旱区生态环境知识资源中心(Arid): A novel heterozygous missense variant of the ARID4A gene identified in Han Chinese families with schizophrenia-diagnosed siblings that interferes with DNA-binding activity

Arid

DOI	10.1038/s41380-022-01530-w
	A novel heterozygous missense variant of the ARID4A gene identified in Han Chinese families with schizophrenia-diagnosed siblings that interferes with DNA-binding activity
	Ren, Decheng; Wei, Xiaoxi; Lin, Lin; Yuan, Fan; Bi, Yan; Guo, Zhenming; Liu, Liangjie; Ji, Lei; Yang, Xiao; Han, Ke; Yang, Fengping; Wu, Xi; Li, Xingwang; Yi, Zhenghui; Xu, Yifeng; Cai, Changqun; Wang, Peng; Li, Weidong; He, Lin; Zhou, Daizhan; Yu, Tao; Shi, Yi; Lu, Qing; He, Guang
通讯作者	Lu, Q ; He, G
来源期刊	MOLECULAR PSYCHIATRY
ISSN	1359-4184
EISSN	1476-5578
出版年	2022
卷号	27 期号:6 页码:2777-2786
英文摘要	ARID4A plays an important role in regulating gene expression and cell proliferation. ARID4A belongs to the AT-rich interaction domain (ARID)-containing family, and a PWWP domain immediately precedes its ARID region. The molecular mechanism and structural basis of ARID4A are largely unknown. Whole-exome sequencing (WES) revealed that a novel heterozygous missense variant, ARID4A c.1231 C > G (p.His411Asp), was associated with schizophrenia (SCZ) in this study. We determined the crystal structure of the PWWP-ARID tandem at 2.05 angstrom, revealing an unexpected mode in which ARID4A assembles with its PWWP and ARID from a structural and functional supramodule. Our results further showed that compared with the wild type, the p.His411Asp ARID mutant protein adopts a less compact conformation and exhibits a weaker dsDNA-binding ability. The p.His411Asp mutation decreased the number of cells that were arrested in the G0-G1 phase and caused more cells to progress to the G2-M phase. In addition, the missense mutation promoted the proliferation of HEK293T cells. In conclusion, our data provide evidence that ARID4A p.His411Asp could cause a conformational change in the ARID4A ARID domain, influence the DNA binding function, and subsequently disturb the cell cycle arrest in the G1 phase. ARID4A is likely a susceptibility gene for SCZ; thus, these findings provide new insight into the role of ARID4A in psychiatric disorders.
类型	Article
语种	英语
收录类别	SCI-E
WOS记录号	WOS:000777289500010
WOS关键词	RBP1 RECRUITS ; TUDOR DOMAIN ; EXPRESSION ; PROTEINS ; REPRESSION ; MUTATIONS ; COMPLEX ; GROWTH ; CHROMO
WOS类目	Biochemistry & Molecular Biology ; Neurosciences ; Psychiatry
WOS研究方向	Biochemistry & Molecular Biology ; Neurosciences & Neurology ; Psychiatry
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/393813
推荐引用方式 GB/T 7714	Ren, Decheng,Wei, Xiaoxi,Lin, Lin,et al. A novel heterozygous missense variant of the ARID4A gene identified in Han Chinese families with schizophrenia-diagnosed siblings that interferes with DNA-binding activity[J],2022,27(6):2777-2786.
APA	Ren, Decheng.,Wei, Xiaoxi.,Lin, Lin.,Yuan, Fan.,Bi, Yan.,...&He, Guang.(2022).A novel heterozygous missense variant of the ARID4A gene identified in Han Chinese families with schizophrenia-diagnosed siblings that interferes with DNA-binding activity.MOLECULAR PSYCHIATRY,27(6),2777-2786.
MLA	Ren, Decheng,et al."A novel heterozygous missense variant of the ARID4A gene identified in Han Chinese families with schizophrenia-diagnosed siblings that interferes with DNA-binding activity".MOLECULAR PSYCHIATRY 27.6(2022):2777-2786.