RESUMO
Germ cells use both positive and negative mRNA translational control to regulate gene expression that drives their differentiation into gametes. mRNA translational control is mediated by RNA-binding proteins, miRNAs and translation initiation factors. We have uncovered the discrete roles of two translation initiation factor eIF4E isoforms (IFE-1, IFE-3) that bind 7-methylguanosine (m7G) mRNA caps during Caenorhabditiselegans germline development. IFE-3 plays important roles in germline sex determination (GSD), where it promotes oocyte cell fate and is dispensable for spermatogenesis. IFE-3 is expressed throughout the germline and localizes to germ granules, but is distinct from IFE-1 and PGL-1, and facilitates oocyte growth and viability. This contrasts with the robust expression in spermatocytes of IFE-1, the isoform that resides within P granules in spermatocytes and oocytes, and promotes late spermatogenesis. Each eIF4E is localized by its cognate eIF4E-binding protein (IFE-1:PGL-1 and IFE-3:IFET-1). IFE-3 and IFET-1 regulate translation of several GSD mRNAs, but not those under control of IFE-1. Distinct mutant phenotypes, in vivo localization and differential mRNA translation suggest independent dormant and active periods for each eIF4E isoform in the germline.
Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Fator de Iniciação 4E em Eucariotos/genética , Masculino , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro , Proteínas de Ligação a RNARESUMO
Large cytoplasmic ribonucleoprotein germ granule complexes are a common feature in germ cells. In C. elegans these are called P granules and for much of the life-cycle they associate with nuclear pore complexes in germ cells. P granules are rich in proteins that function in diverse RNA pathways. Here we report that the C. elegans homolog of the eIF4E-transporter IFET-1 is required for oogenesis but not spermatogenesis. We show that IFET-1 is required for translational repression of several maternal mRNAs in the distal gonad and functions in conjunction with the broad-scale translational regulators CGH-1, CAR-1 and PATR-1 to regulate germ cell sex determination. Furthermore we have found that IFET-1 localizes to P granules throughout the gonad and in the germ cell lineage in the embryo. Interestingly, IFET-1 is required for the normal ultrastructure of P granules and for the localization of CGH-1 and CAR-1 to P granules. Our findings suggest that IFET-1 is a key translational regulator and is required for normal P granule formation.
Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiologia , Grânulos Citoplasmáticos/metabolismo , Células Germinativas/fisiologia , Poro Nuclear/metabolismo , Proteínas Repressoras/metabolismo , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Células Cultivadas , Fator de Iniciação 4E em Eucariotos/genética , Mutação/genética , Oogênese/genética , Biossíntese de Proteínas , Transporte Proteico , RNA Nucleotidiltransferases/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas Repressoras/genética , Homologia de Sequência de Aminoácidos , Processos de Determinação SexualRESUMO
Germ granules are an evolutionarily conserved feature of germ cell cytoplasm and are critical for gametogenesis and embryonic development. Germ granules are highly enriched for RNA and RNA-binding proteins and are key centers for post-transcriptional gene regulation in germ cells. Over the last 20 years, the molecular events in germ granule function and formation in several organisms have begun to be revealed. This review seeks to give an overview of some conserved features of germ granules and highlights a conserved strategy for regulating translation of maternal mRNAs.
