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Control of fetal growth and neonatal survival by the RasGAP-associated endoribonuclease G3BP

Zekri, L.; Chebli, K.; Tourriere, H.; Nielsen, F. C.; Hansen, T. V.; Rami, A.; Tazi, J.

Mol Cell Biol

2005-10 / vol 25 / pages 8703-16

Abstract

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.

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Tags

Female; Animals; Cell Proliferation; Mice; Signal Transduction; Mice, Knockout; Male; *Gene Expression Regulation, Developmental; Alleles; Models, Genetic; Immunoprecipitation; Reverse Transcriptase Polymerase Chain Reaction; Fibroblasts/metabolism; Time Factors; Genotype; Oligonucleotide Array Sequence Analysis; RNA, Messenger/metabolism; Kinetics; Recombination, Genetic; Apoptosis; Genetic Vectors; Recombinant Proteins/chemistry; In Situ Hybridization; Carrier Proteins/metabolism/*physiology; Cell Death; Central Nervous System/metabolism; Dactinomycin/pharmacology; Heterozygote; Neurons/metabolism; Proteome

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