A large imprinted microRNA gene cluster at the mouse Dlkl-Gtl2 domain

A large imprinted microRNA gene cluster at the mouse Dlkl-Gtl2 domain
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DOI:
10.1101/gr.2743304
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发表时间:
2004-09-01
期刊:
影响因子:
7
通讯作者:
Cavaillé, J
Cavaillé, J
中科院分区:
生物学1区
文献类型:
--
作者:
Seitz, H;Royo, H;Cavaillé, J

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MicroRNAs(或miRNAs)是由较长的发夹RNA前体加工而成的小的非编码RNA(21到25个核苷酸),被认为参与了广泛的发育和细胞过程,通过抑制翻译或引发mRNA降解(RNA干扰)。通过使用计算机辅助的方法,我们已经确定了46个潜在的miRNA基因,位于人类印记的14q32结构域,其中40个被组织成一个大簇。虽然这些聚集的miRNA基因中的一些似乎是由单拷贝DNA序列编码的,但它们中的大多数是以密切相关的序列的串联阵列排列的。在小鼠中,这个miRNA基因簇在同源的远端12区是保守的。在体内,我们检测到的所有miRNAs都在发育中的胚胎(头部和躯干)和胎盘中表达,而在成人中,它们的表达主要限于大脑。我们还表明,miRNA基因只在母系遗传的染色体上表达,它们的印记表达受到一个基因间生殖系衍生的差异甲基化区域(IG-DMR)的调控,该区域位于miRNA簇上游类似于200kb的位置。这些似乎只在哺乳动物中保守的miRNAs的功能,从表观遗传控制和发育过程中的基因调控两个方面进行了讨论。
microRNAs (or miRNAs) are small noncoding RNAs (21 to 25 nucleotides) that are processed from longer hairpin RNA precursors and are believed to be involved in a wide range of developmental and cellular processes, by either repressing translation or triggering mRNA degradation (RNA interference). By using a computer-assisted approach, we have identified 46 potential miRNA genes located in the human imprinted 14q32 domain, 40 of which are organized as a large Cluster. Although some of these Clustered miRNA genes appear to be encoded by a single-copy DNA sequence, most of them are arranged in tandem arrays of closely related sequences. In the Mouse, this miRNA gene cluster is conserved at the homologous distal 12 region. In vivo all the miRNAs that we have detected are expressed in the developing embryo (both in the head and in the trunk) and in the placenta, whereas in the adult their expression is mainly restricted to the brain. We also show that the miRNA genes are only expressed from the maternally inherited chromosome and that their imprinted expression is regulated by an intergenic germline-derived differentially methylated region (IG-DMR) located similar to200 kb upstream from the miRNA cluster. The functions of these miRNAs, which seem only conserved in mammals, are discussed both in terms of epigenetic control and gene regulation during development.