The non-coding Air RNA is required for silencing autosomal imprinted genes
The non-coding Air RNA is required for silencing autosomal imprinted genes
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DOI：
10.1038/415810a
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发表时间：
2002-02-14
期刊：
影响因子：
64.8
通讯作者：
Barlow, DP
中科院分区：
文献类型：
--
作者：
Sleutels, F;Zwart, R;Barlow, DP
在基因组印记中，常染色体基因的两个亲本等位基因之一通过顺式作用机制在表观遗传学上沉默（1，2）。通过靶向缺失显示，含有三个印记的、母系表达的蛋白质编码基因（Igf 2 r/Slc 22 a2/Slc 22 a3）的400-RNA酶区域的双向沉默子位于3.7个RNA酶的序列中（3-5），该序列还含有印记的、父系表达的非编码Air RNA的启动子（6）。Air的表达与父本等位基因上所有三个基因的抑制相关（5）;然而，Air RNA仅以反义方向重叠这些基因中的一个（6）。在这里，我们通过插入截短96% RNA转录物的多聚腺苷酸化信号来表明，Air RNA是沉默所需的。截短的Air等位基因保持了Air启动子的印迹表达和甲基化，但显示出父本染色体上Igf 2 r/Slc 22 a2/Slc 22 a3基因簇的沉默完全丧失。我们的研究结果表明，非编码RNA在基因组印迹中起着积极的作用。
In genomic imprinting, one of the two parental alleles of an autosomal gene is silenced epigenetically by a cis-acting mechanism(1,2). A bidirectional silencer for a 400-kilobase region that contains three imprinted, maternally expressed protein-coding genes (Igf2r/Slc22a2/Slc22a3) has been shown by targeted deletion to be located in a sequence of 3.7 kilobases(3-5), which also contains the promoter for the imprinted, paternally expressed non-coding Air RNA(6). Expression of Air is correlated with repression of all three genes on the paternal allele(5); however, Air RNA overlaps just one of these genes in an antisense orientation(6). Here we show, by inserting a polyadenylation signal that truncates 96% of the RNA transcript, that Air RNA is required for silencing. The truncated Air allele maintains imprinted expression and methylation of the Air promoter, but shows complete loss of silencing of the Igf2r/Slc22a2/Slc22a3 gene cluster on the paternal chromosome. Our results indicate that non-coding RNAs have an active role in genomic imprinting.