title: ARS2 is a conserved eukaryotic gene essential for early mammalian development.
abstract: Determining the functions of novel genes implicated in cell survival is directly relevant to our understanding of mammalian development and carcinogenesis. ARS2 is an evolutionarily conserved gene that confers arsenite resistance on arsenite-sensitive Chinese hamster ovary cells. Little is known regarding the function of ARS2 in mammals. We report that ARS2 is transcribed throughout embryonic development and is expressed ubiquitously in mouse and human tissues. The mouse ARS2 protein is predominantly localized to the nucleus, and this nuclear localization is ablated in ARS2-null embryos, which in turn die around the time of implantation. After 24 h of culture, ARS2-null blastocysts contained a significantly greater number of apoptotic cells than wild-type or heterozygous blastocysts. By 48 h of in vitro culture, null blastocysts invariably collapsed and failed to proliferate. These data indicate ARS2 is essential for early mammalian development and is likely involved in an essential cellular process. The analysis of data from several independent protein-protein interaction studies in mammals, combined with functional studies of its Arabidopsis ortholog, SERRATE, suggests that this essential process is related to RNA metabolism.
authors: Centre for Biomedical Research, University of Victoria, P.O. Box 3020 Station CSC, Victoria, BC, Canada.
authors: Michael D
authors: MD
authors: Wilson
authors: Diana
authors: D
authors: Wang
authors: Rebecca
authors: R
authors: Wagner
authors: Hilde
authors: H
authors: Breyssens
authors: Marina
authors: M
authors: Gertsenstein
authors: Corrinne
authors: C
authors: Lobe
authors: Xin
authors: X
authors: Lu
authors: Andras
authors: A
authors: Nagy
authors: Robert D
authors: RD
authors: Burke
authors: Ben F
authors: BF
authors: Koop
authors: Perry L
authors: PL
authors: Howard
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001755:Blastocyst / Q000166:cytology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian; D047108:Embryonic Development; D053595:Embryonic Stem Cells / Q000166:cytology; D005057:Eukaryotic Cells; D019143:Evolution, Molecular; D020043:Genes, Essential; D006579:Heterozygote; D006801:Humans; D007668:Kidney / Q000166:cytology; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D010802:Phylogeny; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C527299:SRRT protein, human; C527300:Srrt protein, mouse; D014157:Transcription Factors