RESUMO
BACKGROUND: For a stem cell population to exist over an extended period, a balance must be maintained between self-renewing (proliferating) and differentiating daughter cells. Within the Caenorhabditis elegans germ line, this balance is controlled by a genetic regulatory pathway, which includes the canonical Notch signaling pathway. RESULTS: Genetic screens identified the gene teg-1 as being involved in regulating the proliferation versus differentiation decision in the C. elegans germ line. Cloning of TEG-1 revealed that it is a homolog of mammalian CD2BP2, which has been implicated in a number of cellular processes, including in U4/U6.U5 tri-snRNP formation in the pre-mRNA splicing reaction. The position of teg-1 in the genetic pathway regulating the proliferation versus differentiation decision, its single mutant phenotype, and its enrichment in nuclei, all suggest TEG-1 also functions as a splicing factor. TEG-1, as well as its human homolog, CD2BP2, directly bind to UAF-1 U2AF65, a component of the U2 auxiliary factor. CONCLUSIONS: TEG-1 functions as a splicing factor and acts to regulate the proliferation versus meiosis decision. The interaction of TEG-1 CD2BP2 with UAF-1 U2AF65, combined with its previously described function in U4/U6.U5 tri-snRNP, suggests that TEG-1 CD2BP2 functions in two distinct locations in the splicing cascade.
Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/embriologia , Proteínas de Transporte/metabolismo , Proliferação de Células , Células Germinativas/crescimento & desenvolvimento , Ribonucleoproteínas/metabolismo , Processos de Determinação Sexual , Células-Tronco/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Alelos , Processamento Alternativo , Sequência de Aminoácidos , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Transporte/genética , Diferenciação Celular/genética , Núcleo Celular/metabolismo , Feminino , Células Germinativas/metabolismo , Humanos , Masculino , Meiose/genética , Dados de Sequência Molecular , Mutação , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fatores de Processamento de RNA , Ribonucleoproteínas/genética , Fator de Processamento U2AF , Células-Tronco/citologiaRESUMO
Maintenance of the stem cell population in the C. elegans germline requires GLP-1/Notch signaling. We show that this signaling inhibits the accumulation of the RNA binding protein GLD-1. In a genetic screen to identify other genes involved in regulating GLD-1 activity, we identified mutations in the nos-3 gene, the protein product of which is similar to the Drosophila translational regulator Nanos. Our data demonstrate that nos-3 promotes GLD-1 accumulation redundantly with gld-2, and that nos-3 functions genetically downstream or parallel to fbf, an inhibitor of GLD-1 translation. We show that the GLD-1 accumulation pattern is important in controlling the proliferation versus meiotic development decision, with low GLD-1 levels allowing proliferation and increased levels promoting meiotic entry.