CCR4-NOT Deadenylates mRNA Associated with RNA-Induced Silencing Complexes in Human Cells

	CCR4-NOT Deadenylates mRNA Associated with RNA-Induced Silencing Complexes in Human Cells
	Piao, XH; Zhang, X; Wu, LG; Belasco, JG
刊名	MOLECULAR AND CELLULAR BIOLOGY
	2010
卷号	30 期号:6 页码:1486-1494
通讯作者	Wu, LG (reprint author), CAS, SIBS, Inst Biochem & Cell Biol, State Key Lab Mol Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,lgwu@sibs.ac.cn ; joel.belasco@med.nyu.edu
英文摘要	MicroRNAs (miRNAs) repress gene expression posttranscriptionally by inhibiting translation and by expediting deadenylation so as to trigger rapid mRNA decay. Their regulatory influence is mediated by the protein components of the RNA-induced silencing complex (RISC), which deliver miRNAs and siRNAs to their mRNA targets. Here, we present evidence that CCR4-NOT is the deadenylase that removes poly(A) from messages destabilized by miRNAs in human cells. Overproducing a mutationally inactivated form of either of the catalytic subunits of this deadenylase (CCR4 or CAF1/POP2) significantly impedes the deadenylation and decay of mRNA targeted by a partially complementary miRNA. The same deadenylase initiates the degradation of "off-target" mRNAs that are bound by an imperfectly complementary siRNA introduced by transfection. The greater inhibitory effect of inactive CAF1 or POP2 (versus inactive CCR4) suggests a predominant role for this catalytic subunit of CCR4-NOT in miRNA-or small interfering RNA (siRNA)-mediated deadenylation. These effects of mi/siRNAs and CCR4-NOT can be fully reproduced by directly tethering RISC to mRNA without the guidance of a small RNA, indicating that the ability of RISC to accelerate deadenylation is independent of RNA base pairing. Despite its importance for mi/siRNA-mediated deadenylation, CCR4-NOT appears not to associate significantly with RISC, as judged by the failure of CAF1 and POP2 to coimmunoprecipitate detectably with either the Ago or TNRC6 subunit of RISC, a finding at odds with deadenylase recruitment as the mechanism by which RISC accelerates poly(A) removal.
学科主题	Biochemistry & Molecular Biology; Cell Biology
类目[WOS]	Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]	MIRNA-MEDIATED REPRESSION ; TRANSLATION INITIATION ; CAENORHABDITIS-ELEGANS ; ARGONAUTE PROTEINS ; C-ELEGANS ; GENE ; MICRORNA ; BINDING ; DEGRADATION ; DROSOPHILA
收录类别	SCI
语种	英语
WOS记录号	WOS:000275058100017
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1021]
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	Piao, XH,Zhang, X,Wu, LG,et al. CCR4-NOT Deadenylates mRNA Associated with RNA-Induced Silencing Complexes in Human Cells[J]. MOLECULAR AND CELLULAR BIOLOGY,2010,30(6):1486-1494.
APA	Piao, XH,Zhang, X,Wu, LG,&Belasco, JG.(2010).CCR4-NOT Deadenylates mRNA Associated with RNA-Induced Silencing Complexes in Human Cells.MOLECULAR AND CELLULAR BIOLOGY,30(6),1486-1494.
MLA	Piao, XH,et al."CCR4-NOT Deadenylates mRNA Associated with RNA-Induced Silencing Complexes in Human Cells".MOLECULAR AND CELLULAR BIOLOGY 30.6(2010):1486-1494.