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

线虫生殖细胞中主要细胞质多聚腺苷酸聚合酶 GLD-2 和去腺苷酸酶之间平衡的功能表征。

基本信息

批准号：
169324141
负责人：
Professor Dr. Christian R. Eckmann
金额：
--
依托单位：
Institut für Biologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2010
资助国家：
德国
起止时间：
2009-12-31 至 2020-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/169324141?language=en
关键词：
Functional characterization balance between major

项目摘要

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.

基因表达程序的多水平调控是动物发育和繁殖的重要过程。在mRNA水平上运作的一种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其普遍。其分子基础的一种形式集中在mRNA的3 '端，即腺苷的均聚延伸，其在细胞质中是连接mRNA翻译和衰变两个过程的枢纽。虽然细胞质聚（A）聚合酶（cPAP）延长聚（A）尾，但去腺苷酸酶（DeAd）将其去除。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聚腺苷酸代谢介导的翻译后控制，我们旨在解决该领域的以下主要问题：如何实现多聚腺苷酸化和去腺苷酸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，我们研究了秀丽隐杆线虫的生殖细胞发育。通过将最先进的全局基因表达分析与强大的poly（A）尾长测量和新的体内转基因方案相结合，我们的目标是发现cPAP介导的mRNA调控的分子原理，以及DeAds和cPAP之间的拮抗作用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。