title: A conserved RNA-protein complex component involved in physiological germline apoptosis regulation in C. elegans.
abstract: Two conserved features of oogenesis are the accumulation of translationally quiescent mRNA, and a high rate of stage-specific apoptosis. Little is understood about the function of this cell death. In C. elegans, apoptosis occurring through a specific ;physiological' pathway normally claims about half of all developing oocytes. The frequency of this germ cell death is dramatically increased by a lack of the RNA helicase CGH-1, orthologs of which are involved in translational control in oocytes and decapping-dependent mRNA degradation in yeast processing (P) bodies. Here, we describe a predicted RNA-binding protein, CAR-1, that associates with CGH-1 and Y-box proteins within a conserved germline RNA-protein (RNP) complex, and in cytoplasmic particles in the gonad and early embryo. The CGH-1/CAR-1 interaction is conserved in Drosophila oocytes. When car-1 expression is depleted by RNA interference (RNAi), physiological apoptosis is increased, brood size is modestly reduced, and early embryonic cytokinesis is abnormal. Surprisingly, if apoptosis is prevented car-1(RNAi) animals are characterized by a progressive oogenesis defect that leads rapidly to gonad failure. Elevated germ cell death similarly compensates for lack of the translational regulator CPB-3 (CPEB), orthologs of which function together with CGH-1 in diverse organisms. We conclude that CAR-1 is of critical importance for oogenesis, that the association between CAR-1 and CGH-1 has been conserved, and that the regulation of physiological germ cell apoptosis is specifically influenced by certain functions of the CGH-1/CAR-1 RNP complex. We propose that this cell death pathway facilitates the formation of functional oocytes, possibly by monitoring specific cytoplasmic events during oogenesis.
authors.affiliation: Joslin Diabetes Center and Department of Pathology, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Boag
authors.forename: Akira
authors.initials: A
authors.lastname: Nakamura
authors.forename: T Keith
authors.initials: TK
authors.lastname: Blackwell
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000166:cytology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism / Q000502:physiology*; D017124:Conserved Sequence; D005260:Female; D015801:Helminth Proteins / Q000502:physiology*; D008297:Male; D009865:Oocytes / Q000166:cytology* / Q000502:physiology*; D009866:Oogenesis / Q000502:physiology; D034622:RNA Interference; D012316:RNA Nucleotidyltransferases / Q000378:metabolism; D018510:RNA, Helminth / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000502:physiology*; D012261:Ribonucleoproteins / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C506963:Car-1 protein, C elegans; D015801:Helminth Proteins; D018510:RNA, Helminth; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D012316:RNA Nucleotidyltransferases; C490618:cgh-1 protein, C elegans