Control of fetal growth and neonatal survival by the RasGAP-associated endoribonuclease G3BP
Control of fetal growth and neonatal survival by the RasGAP-associated endoribonuclease G3BP
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DOI：
10.1128/mcb.25.19.8703-8716.2005
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发表时间：
2005-10-01
影响因子：
5.3
通讯作者：
Tazi, J
中科院分区：
文献类型：
--
作者：
Zekri, L;Chebli, K;Tazi, J
mRNA稳定性的调节在细胞增殖、分化和发育过程中的基因表达控制中起着重要作用。在这里，我们表明，RasGAP相关的核糖核酸内切酶（G3 BP）编码基因的失活导致胚胎死亡和生长迟缓。存活至足月的G3 BP（-/-）小鼠表现出中枢神经系统中凋亡性细胞死亡增加和新生儿致死率增加。在小鼠胚胎成纤维细胞和发育过程中，G3 BP的缺乏改变了必需生长因子的表达，其中印迹基因产物和生长停滞特异性mRNA是突出的。结果表明，G3 BP通过介导多个印迹生长调节转录物的协调表达对胚胎的正常生长和发育至关重要。
The regulation of mRNA stability plays a major role in the control of gene expression during cell proliferation, differentiation, and development. Here, we show that inactivation of the RasGAP-associated endoribonuclease (G3BP)-encoding gene leads to embryonic lethality and growth retardation. G3BP(-/-) mice that survived to term exhibited increased apoptotic cell death in the central nervous system and neonatal lethality. Both in mouse embryonic fibroblasts and during development, the absence of G3BP altered the expression of essential growth factors, among which imprinted gene products and growth arrest-specific mRNAs were outstanding. The results demonstrate that G3BP is essential for proper embryonic growth and development by mediating the coordinate expression of multiple imprinted growth-regulatory transcripts.