Zekri Latifa, Chebli Karim, Tourrière Hélène, Nielsen Finn C, Hansen Thomas V O, Rami Abdelhaq, Tazi Jamal
Institut de Génétique Moléculaire de Montpellier UMR 5535, IFR 122, Centre National de Recherche Scientifique, 1919 route de Mende, 34293 Montpellier, France.
Mol Cell Biol. 2005 Oct;25(19):8703-16. doi: 10.1128/MCB.25.19.8703-8716.2005.
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.
mRNA稳定性的调控在细胞增殖、分化和发育过程中的基因表达控制中起着重要作用。在此,我们表明,编码RasGAP相关核糖核酸内切酶(G3BP)的基因失活会导致胚胎致死和生长迟缓。存活至足月的G3BP-/-小鼠在中枢神经系统中表现出凋亡细胞死亡增加以及新生期致死。在小鼠胚胎成纤维细胞和发育过程中,G3BP的缺失均改变了必需生长因子的表达,其中印记基因产物和生长停滞特异性mRNA尤为突出。结果表明,G3BP通过介导多种印记生长调节转录本的协调表达,对胚胎的正常生长和发育至关重要。