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C. elegans Germline Defense Against Retrotransposons

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dc.contributor.advisor Priess, James R en_US Dennis, Shannon Marie en_US 2012-09-13T17:34:49Z 2012-09-13 2012 en_US
dc.identifier.other Dennis_washington_0250E_10680.pdf en_US
dc.description Thesis (Ph.D.)--University of Washington, 2012 en_US
dc.description.abstract Nematodes appear to have efficient defenses against the germline activity of retroviruses and retrotransposons, as evidenced by the small number of sequences in their genome derived from such elements. No viruses that infect the <italic>C. elegans</italic> germline have been discovered, nor has the presence of virus-like particles (VLPs) been previously reported in germ cells. Retroelements that infect non-dividing cells must access the nucleus via nuclear pores, and in nematode germ cells the majority of nuclear pores are clustered under ribonucleoprotein particles called P granules. In order to determine how retroelements confront or circumvent P granules, we first searched for strains with germline VLPs. We surveyed 16 wild strains of <italic>C. elegans</italic> and 4 additional <italic>Caenorhabditis</italic> species using electron microscopy. We discovered VLPs in the germlines of <italic>C. japonica</italic> and a few <italic>C. elegans</italic> strains, including the lab wild-type strain N2. Using RNA interference to knock-down candidate retrotransposons, we determined that the <italic>C. elegans</italic> VLPs are the product of Cer1, a Ty3/Gypsy class LTR retrotransposon. Expression of Cer1 is both temperature- and age-dependent. In conditions where Cer1 is abundantly expressed it contributes to programmed cell deaths that occur normally during germline development. The distribution of germline VLPs differed between <italic>C. japonica</italic> and <italic>C. elegans</italic>, suggesting different strategies for accumulation near the nucleus, were they might encounter free nuclear pores. In <italic>C. japonica</italic>, we found VLPs in clusters near P granules, indicating they may aggregate near P granules to gain nuclear proximity. In <italic>C. elegans</italic>, in contrast, the VLPs only accumulated near the nuclear envelope (NE) in post-pachytene germ cells, where P granule-free nuclear pores are being added to the NE. Additionally, <italic>C. elegans</italic> VLPs show a strong association with microtubules (MTs), and wild-type localization of VLPs is dynein-dependent. We propose that the <italic>C. elegans</italic> VLPs bind to MTs in order to resist cytoplasmic flow and probe for free nuclear pores. The studies described here provide a foundation for using the model <italic>C. elegans</italic> to study host-pathogen interactions between retroelements and germ cells. en_US
dc.format.mimetype application/pdf en_US
dc.language.iso en_US en_US
dc.rights Copyright is held by the individual authors. en_US
dc.subject en_US
dc.subject.other Molecular biology en_US
dc.subject.other Developmental biology en_US
dc.subject.other Virology en_US
dc.subject.other Molecular and cellular biology en_US
dc.title C. elegans Germline Defense Against Retrotransposons en_US
dc.type Thesis en_US
dc.embargo.terms Restrict to UW for 2 years -- then make Open Access en_US
dc.embargo.lift 2014-09-03T17:34:49Z

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