The GLD-2/-3 cytoplasmic poly(A) polymerase complex and its mRNA targets in C. elegans germ cells

许多发育决定依赖于转录后控制。我们在生殖细胞命运决定方面的工作发现了新的和保守的RNA调节因子。目前的情况是，由翻译抑制物和激活物组成的分子网络通过调节mRNAs来决定细胞的命运，mRNAs编码配子发生分化程序所需的关键细胞命运决定因素和基因产物。虽然靶RNA可能根据细胞命运的不同而不同，但组装的RNP复合体包含一个核心蛋白机制，该机制参与了几乎所有已知的生殖细胞命运决定。我们建议继续我们之前对GLD-2型细胞质聚(A)聚合酶(Cyto-PAP)及其调节蛋白多KH结构域蛋白GLD-3的研究。我们发现细胞质中的多聚腺苷化元件结合蛋白(CPEB)CPB-3是GLD-2/-3复合体的一个组成部分，并且这三种蛋白都与CPB-3mRNA有关。我们建议详细研究CPB-3mRNA的调控，并阐明CPB-3对GLD-2活性的机制作用。我们还建议继续分析GLD-2/-3靶mRNAs，我们在无偏见的屏幕上分离出这些mRNAs。我们的实验旨在为GLD-2 PAPS的分子功能提供新的见解，并将揭示其一些分子靶点及其在生殖系发育中的作用。

Many developmental decisions depend on posttranscriptional controls. Our work on germ cell fate decisions identified novel and conserved RNA regulators. The emerging picture is that a molecular network of translational repressors and activators executes cell fate decisions by regulating mRNAs, encoding key cell fate determinants and gene products required for the gametogenic differentiation program. While target mRNAs may differ depending on the cell fate, the assembling RNP complexes contain a core proteinmachinery that is involved in almost all known germ cell fate decisions. We propose to continue our previous studies on the GLD-2-type cytoplasmic poly(A) polymerase (cyto-PAP) and its regulator, the multi-KH domain protein GLD-3. We found evidences that the cytoplasmic polyadenylation element binding protein (CPEB), CPB-3, as a component of a GLD-2/-3 complex and that all three proteins associate with cpb-3 mRNA. We propose to study the regulation of cpb-3 mRNA in detail and will elucidate the mechanistic roles of CPB- 3 for GLD-2 activity. We also propose to continue our analysis of GLD-2/-3 target mRNAs, which we isolated in an unbiased screen. Our experi-ments aim to provide new insights into the molecular function of GLD-2 PAPs and will reveal some of its molecular targets and their role in germ line development.