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

• Applicant: Professor Dr. Christian R. Eckmann
• Subject Area: Developmental Biology
• Term: from 2010 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 169324141

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.

• DFG Programme: Research Grants