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dc.contributor.advisorBennett, Karen L.eng
dc.contributor.authorOrsborn, April Marie, 1978-eng
dc.date.issued2006eng
dc.date.submitted2006 Summereng
dc.descriptionThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.eng
dc.descriptionThesis (Ph. D.) University of Missouri-Columbia 2006.eng
dc.descriptionVita.eng
dc.description.abstractThe Caenorhabditis elegans germline RNA helicases (GLHs) are constitutive components of P granules, non-membranous aggregates of protein and RNA that segregate with the nematode germline. The GLHs are critical for fertility. The novel MAP kinase, KGB-1, interacts with the GLH proteins, and the null kgb-1(um3) strain results in sterile worms at high temperatures; the germlines of these worms contain endomitotic replicating oocytes (EMO). We find that in kgb-1(um3) adults, while GLH-4 levels are similar to wild type, levels of GLH-1 are increased up to seven fold and the morphology of P granules is grossly affected. Binding of KGB-1 to GLH-1 requires a MAP kinase docking site. KGB-1 can phosphorylate GLH-1 using in vitro kinase assays, and GLH-1 is degraded by the proteasome in a KGB-1-dependent manner. In addition, KGB-1 physically associates with CSN-5 (COP9 signalosome subunit 5), another GLH binding partner. RNA interference (RNAi) of csn-5 results in sterile worms with under-proliferated germlines, mirroring the combined glh-1 and glh-4 RNAi phenotype. In contrast, elimination of csn-5 in the kgb-1(um3) background results in significantly more fertile worms than in non-injected kgb-1 worms. Based on these biochemical and genetic interactions, we propose KGB-1 and CSN-5 may oppositely regulate GLH-1, with KGB-1 degrading and CSN-5 protecting GLH-1. This cooperative system could maintain proper GLH-1 levels during normal germline development, as well as prevent excess GLH accumulation during the stressful conditions of high temperature and aging.eng
dc.description.bibrefIncludes bibliographical referenceseng
dc.identifier.merlinb66330142eng
dc.identifier.oclc309296428eng
dc.identifier.urihttps://doi.org/10.32469/10355/4499eng
dc.identifier.urihttps://hdl.handle.net/10355/4499
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcommunityUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.rightsOpenAccess.eng
dc.subject.meshCytoplasmic Granuleseng
dc.subject.meshJNK Mitogen-Activated Protein Kinases -- metabolismeng
dc.subject.meshGerm Cells -- enzymologyeng
dc.subject.meshCaenorhabditis elegans Proteins -- metabolismeng
dc.subject.meshDEAD-box RNA Helicases -- metabolismeng
dc.titleAnalysis of interactions between the germline RNA helicases (GLHs) and their regulators KGB-1 and CSN-5 in Caenorhabditis eleganseng
dc.typeThesiseng
thesis.degree.disciplineMicrobiology (Medicine) (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


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