Regulation of transposon mobilization in Caenorhabditis elegans

Abstract

Transposons are parasitic nucleic acids widespread in eukaryotic genomes. They have the ability to mobilize within the genome and are present at high copy numbers, thereby posing a significant threat to the genome stability of organisms. All eukaryotic systems have mechanisms to silence transposons. However, our understanding of these mechanisms is not complete. Forward genetic screens in Caenorhabditis elegans have identified regulators of transposon silencing, but these screens were not saturated, were limited to looking at transposon regulation in the germline, and many identified transposon regulators remain uncharacterized mechanistically. My dissertation work focuses on identifying novel mechanisms of transposon regulation in C. elegans. In Chapter 2, I describe an in vivo live animal reporter system that we developed to study transposon mobilization. I use this system to identify new germline transposon silencing factors, which include nuclear and cytoplasmic RNAi pathway factors. I show that germline transposon silencing factors do not silence soma transposons. I establish that the 1000-fold rate difference between soma and germline transposon mobilization in C. elegans is largely explained by the differing choice of DNA repair pathway in these two tissue types. In Chapter 3, I describe an unbiased genetic screen that identifies three novel factors that regulate soma transposon mobilization in C. elegans.