Dynamic developmental regulation of the large non-coding RNA associated with the mouse 7C imprinted chromosomal region
Dynamic developmental regulation of the large non-coding RNA associated with the mouse 7C imprinted chromosomal region
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DOI：
10.1016/j.ydbio.2005.07.030
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发表时间：
2005-10-15
影响因子：
2.7
通讯作者：
Muscatelli, F
中科院分区：
文献类型：
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作者：
Le Meur, E;Watrin, F;Muscatelli, F
Prader-Willi/Angelman综合征印迹结构域的小鼠直系同源物包含几个父系特异性转录本和编码泛素蛋白连接酶E3 A（Ube 3a）的母系表达基因。一个大的父系非编码RNA，包括Snurf-Snrpn外显子和Ube 3a反义转录本（Ube 3a-ATS），最近已被表征并命名为LNCAT。LNCAT在印迹、基因调控和疾病中的潜在作用可能是但尚未研究。为了确定LNCAT的功能，我们首先确定了其在体内的时空表达模式，在细胞水平上的发展过程中，并在不同的成人脑组织中，我们在这里显示，LNCAT的发育调控，转录变体通过有丝分裂后神经元的神经元分化特异性表达。我们表明，LNCAT和Snurf-Snrpn成绩单是独立的，虽然他们有共同的外显子。我们发现，通过配子发生和早期胚胎排除LNCAT的作用，在印记建立LNCAT的表达的情况下。我们还报告了一系列的观察，挑战了广泛接受的模式Ube 3a的印迹基因沉默。尽管这些最后的数据并不完全排除包括“Ube 3a-ATS”外显子的LNCAT变体可以抑制Ube 3a的父系等位基因，但它们确实允许我们提出替代的和一致的模型。(C)2005年爱思唯尔公司All rights reserved.
The mouse ortholog of the Prader-Willi/Angelman syndrome imprinted domain contains several paternal-specific transcripts and the maternally expressed gene encoding ubiquitin protein ligase E3A (Ube3a). A Large paternal Non-Coding RNA, encompassing Snurf-Snrpn exons and the Ube3a Antisense Transcript (Ube3a-ATS), has been recently characterized and named here LNCAT Potential roles of LNCAT in imprinting, gene regulation, and disease are likely but have not been investigated. In order to establish the function(s) of LNCAT, we first determined its in vivo spatio-temporal expression pattern at the cellular level during development and in different adult brain tissues.We show here that LNCAT is developmentally regulated, with transcript variants being specifically expressed through neuronal differentiation in postmitotic neurons. We demonstrate that the LNCAT and Snurf-Snrpn transcripts are independent although they share common exons. We show an absence of expression of LNCAT through gametogenesis and in early embryo excluding a role of LNCAT in the imprint establishment. We also report a range of observations that challenges the widely accepted model of imprinted gene silencing of Ube3a. Although these last data do not completely exclude that the LNCAT variants including "Ube3a-ATS" exons could repress the paternal allele of Ube3a, they do allow us to propose an alternative and consistent model. (C) 2005 Elsevier Inc. All rights reserved.