Efficient Translation of Dnmt1 Requires Cytoplasmic Polyadenylation and Musashi Binding Elements

	Efficient Translation of Dnmt1 Requires Cytoplasmic Polyadenylation and Musashi Binding Elements
	Rutledge, CE; Lau, HT; Mangan, H; Hardy, LL; Sunnotel, O; Guo, F; MacNicol, AM; Walsh, CP; Lees-Murdock, DJ
刊名	PLOS ONE
	2014
卷号	9 期号:2 页码:e88385-e88385
通讯作者	Lees-Murdock, DJ (reprint author), Univ Ulster, Transcript Regulat & Epigenet Res Grp, Sch Biomed Sci, Coleraine BT52 1SA, Londonderry, North Ireland.,dj.lees@ulster.ac.uk
英文摘要	Regulation of DNMT1 is critical for epigenetic control of many genes and for genome stability. Using phylogenetic analysis we characterized a block of 27 nucleotides in the 3'UTR of Dnmt1 mRNA identical between humans and Xenopus and investigated the role of the individual elements contained within it. This region contains a cytoplasmic polyadenylation element (CPE) and a Musashi binding element (MBE), with CPE binding protein 1 (CPEB1) known to bind to the former in mouse oocytes. The presence of these elements usually indicates translational control by elongation and shortening of the poly(A) tail in the cytoplasm of the oocyte and in some somatic cell types. We demonstrate for the first time cytoplasmic polyadenylation of Dnmt1 during periods of oocyte growth in mouse and during oocyte activation in Xenopus. Furthermore we show by RNA immunoprecipitation that Musashi1 (MSI1) binds to the MBE and that this element is required for polyadenylation in oocytes. As well as a role in oocytes, site-directed mutagenesis and reporter assays confirm that mutation of either the MBE or CPE reduce DNMT1 translation in somatic cells, but likely act in the same pathway: deletion of the whole conserved region has more severe effects on translation in both ES and differentiated cells. In adult cells lacking MSI1 there is a greater dependency on the CPE, with depletion of CPEB1 or CPEB4 by RNAi resulting in substantially reduced levels of endogenous DNMT1 protein and concurrent upregulation of the well characterised CPEB target mRNA cyclin B1. Our findings demonstrate that CPE-and MBE-mediated translation regulate DNMT1 expression, representing a novel mechanism of post-transcriptional control for this gene.
学科主题	Science & Technology - Other Topics
类目[WOS]	Multidisciplinary Sciences
关键词[WOS]	MESSENGER-RNA TRANSLATION ; XENOPUS OOCYTE MATURATION ; CELL-CYCLE PROGRESSION ; DNA METHYLTRANSFERASE ; CYTOSINE METHYLATION ; POSTMITOTIC NEURONS ; MEIOTIC PROGRESSION ; TEMPORAL CONTROL ; STEM-CELLS ; GERM-CELLS
收录类别	SCI
语种	英语
WOS记录号	WOS:000331714700017
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/136]
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	Rutledge, CE,Lau, HT,Mangan, H,et al. Efficient Translation of Dnmt1 Requires Cytoplasmic Polyadenylation and Musashi Binding Elements[J]. PLOS ONE,2014,9(2):e88385-e88385.
APA	Rutledge, CE.,Lau, HT.,Mangan, H.,Hardy, LL.,Sunnotel, O.,...&Lees-Murdock, DJ.(2014).Efficient Translation of Dnmt1 Requires Cytoplasmic Polyadenylation and Musashi Binding Elements.PLOS ONE,9(2),e88385-e88385.
MLA	Rutledge, CE,et al."Efficient Translation of Dnmt1 Requires Cytoplasmic Polyadenylation and Musashi Binding Elements".PLOS ONE 9.2(2014):e88385-e88385.