Functional characterization of the balance between the major cytoplasmic poly(A) polymerase GLD-2 and deadenylases in C. elegans germ cells.

基因表达程序在多个水平上的调控是动物发育和繁殖所必需的过程。在信使核糖核酸水平上运作的一种关键调控模式被称为转录后调控，这在神经元和生殖细胞中尤其普遍。其分子基础的一种形式是以mRNAs 3基端为中心，这是腺苷的同质聚合延伸，在细胞质中是连接mRNA翻译和衰退两个过程的枢纽。当细胞质多(A)聚合酶(CPAP)拉长多(A)尾巴时，死烯基酶(DEAD)去除它们。通过调节Poly(A)的尾长，这两种相反的酶活性被认为控制了mRNAs的可译性和稳定性。为了在全球范围内了解多聚(A)代谢在生殖细胞发育过程中介导的翻译后调控，我们致力于解决该领域的以下主要问题：如何实现多聚腺苷化和去烯化活性之间的动态平衡，以支持复杂组织的发育和功能。为了解决这些问题，我们研究了秀丽线虫生殖细胞的发育。通过结合最先进的全球基因表达分析、强大的Poly(A)尾长测量和最新可用的体内转基因方案，我们旨在发现CPAP介导的mRNA调控的分子原理，以及DEAD和CPAP之间的拮抗如何调节生殖细胞基因表达程序。这项工作将大大增加我们对Poly(A)介导的控制机制及其对生殖的影响的理解。

The regulation of gene expression programs at multiple levels is an essential process for animal development and reproduction. A key regulatory mode that operates at the mRNA level is known as post-transcriptional control, which is especially prevalent in neurons and germ cells. One form of its molecular basis is centered on the mRNAs 3 prime end, a homo-polymeric stretch of adenosines, which is in the cytoplasm a hub of connecting the two processes of mRNA translation and decay. While cytoplasmic poly(A) polymerases (cPAPs) elongate poly(A) tails, deadenylases (DeAds) remove them. By regulating poly(A) tail length, these two opposing enzymatic activities are presumed to control the translatability and stability of mRNAs. To gain a global understanding of poly(A) metabolism-mediated post- translational control during germ cell development, we aim at resolving the following main question in the field: How is the dynamic balance between polyadenylation and deadenylation activities achieved to support the development and functionality of a complex tissue. To address these questions, we study germ cell development in Caenorhabditis elegans. By combining state-of-the-art global gene expression analysis with powerful poly(A) tail-length measurements and newly available in vivo transgenesis protocols, we aim to discover molecular principles of cPAP-mediated mRNA regulation, and how the antagonism between DeAds and cPAPs regulates germ cell gene expression programs. This work will substantially increase our understanding of poly(A)-mediated control mechanisms and its impact on reproduction.