Control of fetal growth and neonatal survival by the RasGAP-associated endoribonuclease G3BP.
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.
Zekri
Latifa
L
Institut de Génétique Moléculaire de Montpellier UMR 5535, IFR 122, Centre National de Recherche Scientifique, 1919 route de Mende, 34293 Montpellier, France.
Chebli
Karim
K
Tourrière
Hélène
H
Nielsen
Finn C
FC
Hansen
Thomas V O
TV
Rami
Abdelhaq
A
Tazi
Jamal
J
D000483:Alleles; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D016923:Cell Death; D049109:Cell Proliferation; D002490:Central Nervous System / Q000378:metabolism; D004265:DNA Helicases; D003609:Dactinomycin / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005822:Genetic Vectors; D005838:Genotype; D006579:Heterozygote; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D007700:Kinetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D009474:Neurons / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D000075223:Poly-ADP-Ribose Binding Proteins; D020543:Proteome; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors
D002352:Carrier Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D020543:Proteome; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D003609:Dactinomycin; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases