ARS2 Is a Conserved Eukaryotic Gene Essential for Early Mammalian Development

<jats:title>ABSTRACT</jats:title> <jats:p>Determining the functions of novel genes implicated in cell survival is directly relevant to our understanding of mammalian development and carcinogenesis. <jats:italic>ARS2</jats:italic> is an evolutionarily conserved gene that confers arsenite resistance on arsenite-sensitive Chinese hamster ovary cells. Little is known regarding the function of <jats:italic>ARS2</jats:italic> in mammals. We report that <jats:italic>ARS2</jats:italic> 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 <jats:italic>ARS2</jats:italic>-null embryos, which in turn die around the time of implantation. After 24 h of culture, <jats:italic>ARS2</jats:italic>-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 <jats:italic>ARS2</jats:italic> 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 <jats:italic>Arabidopsis</jats:italic> ortholog, <jats:italic>SERRATE</jats:italic>, suggests that this essential process is related to RNA metabolism.</jats:p>