CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, 1090 Vienna, Austria.
Science. 2012 Dec 14;338(6113):1469-72. doi: 10.1126/science.1228110.
Mammalian imprinted genes often cluster with long noncoding (lnc) RNAs. Three lncRNAs that induce parental-specific silencing show hallmarks indicating that their transcription is more important than their product. To test whether Airn transcription or product silences the Igf2r gene, we shortened the endogenous lncRNA to different lengths. The results excluded a role for spliced and unspliced Airn lncRNA products and for Airn nuclear size and location in silencing Igf2r. Instead, silencing only required Airn transcriptional overlap of the Igf2r promoter, which interferes with RNA polymerase II recruitment in the absence of repressive chromatin. Such a repressor function for lncRNA transcriptional overlap reveals a gene silencing mechanism that may be widespread in the mammalian genome, given the abundance of lncRNA transcripts.
哺乳动物印记基因通常与长链非编码 (lnc) RNA 簇集在一起。有 3 种 lncRNA 可诱导亲本特异性沉默，这些 lncRNA 具有表明其转录比其产物更重要的特征。为了测试 Airn 转录或产物是否沉默 Igf2r 基因，我们将内源性 lncRNA 缩短至不同长度。结果排除了剪接和非剪接 Airn lncRNA 产物以及 Airn 核大小和位置在沉默 Igf2r 中的作用。相反，沉默仅需要 Airn 在 Igf2r 启动子上的转录重叠，这会干扰 RNA 聚合酶 II 在没有抑制性染色质的情况下的募集。这种 lncRNA 转录重叠的抑制功能揭示了一种基因沉默机制，鉴于 lncRNA 转录本的丰富性，这种机制可能在哺乳动物基因组中广泛存在。
