ADAR1 is required for differentiation and neural induction by regulating microRNA processing in a catalytically independent manner

	ADAR1 is required for differentiation and neural induction by regulating microRNA processing in a catalytically independent manner
	Chen, T; Xiang, JF; Zhu, SS; Chen, SY; Yin, QF; Zhang, XO; Zhang, J; Feng, H; Dong, R; Li, XJ
刊名	CELL RESEARCH
	2015
卷号	25 期号:4 页码:459-476
关键词	ADAR1 RNA editing embryonic stem cell neural induction miRNA
通讯作者	Yang, L (reprint author), Chinese Acad Sci, CAS Ctr Excellence Brain Sci, CAS MPG Partner Inst Computat Biol, CAS Key Lab Computat Biol,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.,liyang@picb.ac.cn ; linglingchen@sibcb.ac.cn
英文摘要	Adenosine deaminases acting on RNA (ADARs) are involved in adenosine-to-inosine RNA editing and are implicated in development and diseases. Here we observed that ADAR1 deficiency in human embryonic stem cells (hESCs) significantly affected hESC differentiation and neural induction with widespread changes in mRNA and miRNA expression, including upregulation of self-renewal-related miRNAs, such as miR302s. Global editing analyses revealed that ADAR1 editing activity contributes little to the altered miRNA/mRNA expression in ADAR1-deficient hESCs upon neural induction. Genome-wide iCLIP studies identified that ADAR1 binds directly to pri-miRNAs to interfere with miRNA processing by acting as an RNA-binding protein. Importantly, aberrant expression of miRNAs and phenotypes observed in ADAR1-depleted hESCs upon neural differentiation could be reversed by an enzymatically inactive ADAR1 mutant, but not by the RNA-binding-null ADAR1 mutant. These findings reveal that ADAR1, but not its editing activity, is critical for hESC differentiation and neural induction by regulating miRNA biogenesis via direct RNA interaction.
学科主题	Cell Biology
类目[WOS]	Cell Biology
关键词[WOS]	EMBRYONIC STEM-CELLS ; LONG NONCODING RNAS ; ADENOSINE DEAMINASES ; NUCLEAR RETENTION ; INDUCED APOPTOSIS ; EDITING SITES ; HUMAN BRAIN ; GENE ; COMPLEX ; ENZYME
收录类别	SCI
语种	英语
WOS记录号	WOS:000353917200005
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/48]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Chen, T,Xiang, JF,Zhu, SS,et al. ADAR1 is required for differentiation and neural induction by regulating microRNA processing in a catalytically independent manner[J]. CELL RESEARCH,2015,25(4):459-476.
APA	Chen, T.,Xiang, JF.,Zhu, SS.,Chen, SY.,Yin, QF.,...&Chen, LL.(2015).ADAR1 is required for differentiation and neural induction by regulating microRNA processing in a catalytically independent manner.CELL RESEARCH,25(4),459-476.
MLA	Chen, T,et al."ADAR1 is required for differentiation and neural induction by regulating microRNA processing in a catalytically independent manner".CELL RESEARCH 25.4(2015):459-476.