The development of an organism and its adult homeostasis rely on regulatory mechanisms that control the underlying gene expression programs. In certain biological contexts, such as germ cell development, gene expression regulation is largely executed at the post-‐transcriptional level. This relies on RNA-‐binding proteins (RBPs), whose activity and expression are also heavily controlled. While the RNA-‐binding potential of RBPs is currently of intense scrutiny, surprisingly little is known to date about the molecular mechanisms that control RNA-‐binding proteins abundance in the context of germ cell development.
This work identifies the molecular mechanisms that shape expression patterns of two evolutionarily conserved RNA-‐binding proteins, CPB-‐3 and GLD-‐ 1, which belong to CPEB and STAR protein family, respectively. By focusing on their regulation in the C. elegans germ line, this work reveals an involvement of the proteasome in reducing levels of CPB-‐3/CPEB and GLD-‐1/STAR at the pachytene-‐to-‐diplotene transition during meiotic prophase I. Furthermore, it documents that CPB-‐3 and GLD-‐1 are targeted to proteasomal degradation by a conserved SCF ubiquitin ligase complex that utilises SEL-‐10/Fbxw7 as a substrate recognition subunit. Importantly, destabilisation of both RBPs is likely triggered by their phosphorylation, which is regulated by the mitogen-‐activated protein kinase, MPK-‐1, and restricted to the meiotic timepoint of pachytene exit. Lastly, this work investigates the potential consequences of target mRNA regulation upon delayed RBP degradation. Altogether, the collected data characterise a molecular pathway of CPEB and STAR protein turnover, and suggest that MPK-‐1 signaling may couple RBP-‐mediated regulation of gene expression to progression through meiosis during oogenesis.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa.de:bsz:14-qucosa-234186 |
| Date | 17 April 2018 |
| Creators | Kisielnicka, Edyta |
| Contributors | Technische Universität Dresden, Fakultät Mathematik und Naturwissenschaften, Prof. Dr. Christian R. Eckmann, Prof. Dr. Christian Dahmann, Prof. Dr. Elisabeth Knust |
| Publisher | Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | doc-type:doctoralThesis |
| Format | application/pdf |
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