The H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and Igf1r.
The H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and Igf1r.
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DOI：
10.1038/ncb2521
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发表时间：
2012-06-10
影响因子：
21.3
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中科院分区：
文献类型：
--
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H19大基因间非编码RNA(LincRNA)是哺乳动物发育过程中含量最丰富、最保守的转录本之一，在胚胎和胚外细胞中均有表达，但其生理功能尚不清楚。在这里，我们发现miR-675，一种嵌入H19‘S第一外显子的微小RNA(MiRNA)，从胎盘生长正常停止的妊娠时间点开始，仅在胎盘中表达，而缺乏H19的胎盘继续生长。MiR-675在一系列胚胎和胚外细胞系中的过表达导致它们的增殖减少；在H19缺失的胎盘中miRNA的靶标上调，包括促进生长的胰岛素样生长因子1受体(IGF1r)。此外，从H19中删除miR-675的过程是由应激反应RNA结合蛋白Hur动态调节的。这些结果表明，H19‘S的主要生理作用是通过调节miR-675的加工，限制胎盘在出生前的生长。从H19中控制释放miR-675也可能允许快速抑制细胞增殖，以响应细胞应激或致癌信号。
The H19 large intergenic noncoding RNA (lincRNA) is one of the most highly abundant and conserved transcripts in mammalian development, being expressed in both embryonic and extraembryonic cell lineages, yet its physiological function is unknown. Here we show that miR-675, a microRNA (miRNA) embedded within H19’s first exon, is expressed exclusively in the placenta from the gestational time point when placental growth normally ceases, and placentas that lack H19 continue to grow. Overexpression of miR-675 in a range of embryonic and extraembryonic cell lines results in their reduced proliferation; targets of the miRNA are upregulated in the H19 null placenta, including the growth promoting Insulin-like growth factor 1 receptor (Igf1r). Moreover, the excision of miR-675 from H19 is dynamically regulated by the stress response RNA binding protein HuR. These results suggest that H19’s main physiological role is in limiting growth of the placenta prior to birth, by regulated processing of miR-675. The controlled release of miR-675 from H19 may also allow rapid inhibition of cell proliferation in response to cellular stress or oncogenic signals.
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影响因子：
64.8
作者：
HAO, Y;CRENSHAW, T;TYCKO, B
通讯作者：
TYCKO, B
影响因子：
64.5
作者：
BAKER, J;LIU, JP;EFSTRATIADIS, A
通讯作者：
EFSTRATIADIS, A
影响因子：
7
作者：
Knox, Kirstin;Baker, Julie C.
通讯作者：
Baker, Julie C.
影响因子：
64.5
作者：
LIU, JP;BAKER, J;EFSTRATIADIS, A
通讯作者：
EFSTRATIADIS, A
影响因子：
3.8
作者：
Esquiliano DR;Guo W;Liang L;Dikkes P;Lopez MF
通讯作者：
Lopez MF