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确定了新的和保守的RNA调节子。新出现的图像是，翻译抑制因子和激活因子的分子网络通过调节mRNA，编码配子发生分化程序所需的关键细胞命运决定因子和基因产物来执行细胞命运决定。虽然靶mRNA可能因细胞命运而异，但组装的RNP复合物包含一个核心蛋白质机制，该机制参与几乎所有已知的生殖细胞命运决定。我们建议继续我们以前的研究，GLD-2型细胞质多聚（A）聚合酶（细胞PAP）及其调节剂，多KH结构域蛋白GLD-3。我们发现的证据表明，细胞质多聚腺苷酸化元件结合蛋白（CPEB），CPB-3，作为一个组成部分的GLD-2/-3复合物，所有三个蛋白质与cpb-3 mRNA。我们建议详细研究CPB-3 mRNA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我们在无偏筛选中分离的GLD-2/-3靶mRNA。我们的实验旨在为GLD-2 PAP的分子功能提供新的见解，并将揭示其一些分子靶标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.