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的重要过程。在mRNA水平上起作用的一个关键调控模式被称为转录后控制，这在神经元和生殖细胞中尤为普遍。其分子基础的一种形式以mRNA 3 '端为中心，这是一段腺苷的同聚延伸，在细胞质中是连接mRNA翻译和衰变两个过程的枢纽。当细胞质聚(A)聚合酶（cpap）延长聚(A)尾部时，死烯化酶（DeAds）去除它们。通过调节poly(A)尾长度，这两种相反的酶活性被认为控制mrna的可翻译性和稳定性。为了全面了解生殖细胞发育过程中多(a)代谢介导的翻译后控制，我们的目标是解决该领域的以下主要问题：多聚腺苷化和死烯化活性之间的动态平衡是如何实现的，以支持复杂组织的发育和功能。为了解决这些问题，我们研究了秀丽隐杆线虫的生殖细胞发育。通过结合最先进的全球基因表达分析、强大的聚(A)尾长测量和最新的体内转基因方案，我们旨在发现cpap介导的mRNA调控的分子原理，以及DeAds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多聚(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.