A Novel H19 Antisense RNA Overexpressed in Breast Cancer Contributes to Paternal IGF2 Expression
A Novel H19 Antisense RNA Overexpressed in Breast Cancer Contributes to Paternal IGF2 Expression
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DOI：
10.1128/mcb.02103-07
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发表时间：
2008-11-15
影响因子：
5.3
通讯作者：
Adriaenssens, Eric
中科院分区：
文献类型：
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作者：
Berteaux, Nathalie;Aptel, Nathalie;Adriaenssens, Eric
H19/IGFf2 基因座属于位于人类染色体 11p15.5（与小鼠远端 7 号染色体同源）上的一个大印记结构域。 H19 基因由母本等位基因表达，而 IGF2 由父本等位基因表达。天然反义转录物和基因间转录已涉及真核基因表达的许多方面，包括基因组印记和RNA干扰。然而，除了一些 IGF2 反义转录本的鉴定之外，关于 H19/IGF2 基因座的该主题的可用数据很少。我们在此鉴定了人类和小鼠 H19/IGF2 印记位点的新转录活性。这种活性与 H19 基因反义，有可能产生一个 120 kb 的转录物，我们称之为 91H RNA。这种核内的短寿命 RNA 在小鼠体内没有印记，但主要由小鼠和人类 H19 基因区域内的母体等位基因表达。此外，该转录物在乳腺癌细胞中稳定，并在人类乳腺肿瘤中过度表达。最后，敲低实验表明，在人类中，91H 不是影响 H19 的表达，而是调节反式 IGF2 的表达。
The H19/IGFf2 locus belongs to a large imprinted domain located on human chromosome 11p15.5 ( homologue to mouse distal chromosome 7). The H19 gene is expressed from the maternal allele, while IGF2 is paternally expressed. Natural antisense transcripts and intergenic transcription have been involved in many aspects of eukaryotic gene expression, including genomic imprinting and RNA interference. However, apart from the identification of some IGF2 antisense transcripts, few data are available on that topic at the H19/IGF2 locus. We identify here a novel transcriptional activity at both the human and the mouse H19/IGF2 imprinted loci. This activity occurs antisense to the H19 gene and has the potential to produce a single 120-kb transcript that we called the 91H RNA. This nuclear and short-lived RNA is not imprinted in mouse but is expressed predominantly from the maternal allele in both mice and humans within the H19 gene region. Moreover, the transcript is stabilized in breast cancer cells and overexpressed in human breast tumors. Finally, knockdown experiments showed that, in humans, 91H, rather than affecting H19 expression, regulates IGF2 expression in trans.