Topoisomerase 3 beta is the major topoisomerase for mRNAs and linked to   neurodevelopment and mental dysfunction

doi:10.1093/nar/gkw1293

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	Topoisomerase 3 beta is the major topoisomerase for mRNAs and linked to neurodevelopment and mental dysfunction
	Ahmad, Muzammil ; Shen, Weiping ; Li, Wen ; Xue, Yutong ; Zou, Sige ; Xu, Dongyi ; Wang, Weidong
刊名	NUCLEIC ACIDS RESEARCH
	2017
关键词	FRAGILE-X-SYNDROME DNA TOPOISOMERASES BINDING PROTEINS III-BETA SCHIZOPHRENIA TOP3-BETA FMRP PERSPECTIVE AUTISM ROLES
DOI	10.1093/nar/gkw1293
英文摘要	Human cells contain five topoisomerases in the nucleus and cytoplasm, but which one is the major topoisomerase for mRNAs is unclear. To date, Top3 beta is the only known topoisomerase that possesses RNA topoisomerase activity, binds mRNA translation machinery and interacts with an RNA-binding protein, FMRP, to promote synapse formation; and Top3 beta gene deletion has been linked to schizophrenia. Here, we show that Top3 beta is also the most abundant mRNA-binding topoisomerase in cells. Top3 beta, but not other topoisomerases, contains a distinctive RNA-binding domain; and deletion of this domain diminishes the amount of Top3 beta that associates with mRNAs, indicating that Top3 beta is specifically targeted to mRNAs by its RNA binding domain. Moreover, Top3 beta mutants lacking either its RNA-binding domain or catalytic residue fail to promote synapse formation, suggesting that Top3 beta requires both its mRNA-binding and catalytic activity to facilitate neurodevelopment. Notably, Top3 beta proteins bearing point mutations from schizophrenia and autism individuals are defective in association with FMRP; whereas one of the mutants is also deficient in binding mRNAs, catalyzing RNA topoisomerase reaction, and promoting synapse formation. Our data suggest that Top3 beta is the major topoisomerase for mRNAs, and requires both RNA binding and catalytic activity to promote neurodevelopment and prevent mental dysfunction.; National Institutes of Health [Z01 AG00065708]; National Basic Research Program of China [2013CB911002]; National Natural Science Foundation of China [31271435]; SCI(E); SSCI; ARTICLE; 5; 2704-2713; 45
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/469313]
专题	生命科学学院
推荐引用方式 GB/T 7714	Ahmad, Muzammil,Shen, Weiping,Li, Wen,et al. Topoisomerase 3 beta is the major topoisomerase for mRNAs and linked to neurodevelopment and mental dysfunction[J]. NUCLEIC ACIDS RESEARCH,2017.
APA	Ahmad, Muzammil.,Shen, Weiping.,Li, Wen.,Xue, Yutong.,Zou, Sige.,...&Wang, Weidong.(2017).Topoisomerase 3 beta is the major topoisomerase for mRNAs and linked to neurodevelopment and mental dysfunction.NUCLEIC ACIDS RESEARCH.
MLA	Ahmad, Muzammil,et al."Topoisomerase 3 beta is the major topoisomerase for mRNAs and linked to neurodevelopment and mental dysfunction".NUCLEIC ACIDS RESEARCH (2017).