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Molecular and Cellular Biology, October 2005, p. 8703-8716, Vol. 25, No. 19
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.19.8703-8716.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Control of Fetal Growth and Neonatal Survival by the RasGAP-Associated Endoribonuclease G3BP

Latifa Zekri,^1, Karim Chebli,^1, Hélène Tourrière,¹ Finn C. Nielsen,² Thomas V. O. Hansen,² Abdelhaq Rami,³ and Jamal Tazi^1*

Institut de Génétique Moléculaire de Montpellier UMR 5535, IFR 122, Centre National de Recherche Scientifique, 1919 Route de Mende, 34293 Montpellier, France,¹ Department of Clinical Biochemistry, University Hospital Rigshospitalet, University of Copenhagen, Copenhagen, Denmark,² Anatomisches Institut III, Uniklinik, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany³

Received 6 April 2005/ Returned for modification 6 May 2005/ Accepted 6 July 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.

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* Corresponding author. Mailing address: Institut de Génétique Moléculaire de Montpellier UMR 5535, IFR 122, Centre National de Recherche Scientifique, 1919 route de Mende, 34293 Montpellier, France. Phone: 33 (0) 4 67 61 36 85. Fax: 33 (0) 4 67 04 02 45. E-mail: jamal.tazi{at}igmm.cnrs.fr.

Latifa Zekri and Karim Chebli contributed equally to this work.

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Molecular and Cellular Biology, October 2005, p. 8703-8716, Vol. 25, No. 19
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.19.8703-8716.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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