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Investigation of the roX RNAs and the RNA Helicase MLE in Dosage Compensation in Drosophila melanogaster

dc.contributor.advisor Amrein, Hubert O Hendricks, Dianne Grayce 2010-05-10T19:55:33Z 2010-05-10T19:55:33Z 2009
dc.description.abstract <p>In Drosophila melanogaster, where males are XY and females are XX, dosage compensation is acheived by approximately two-fold upregulation of transcription of the single male X chromosome. This upregulation is mediated by the dosage compensation complex (DCC), which is assembled in a sequential manner on the male X chromosome and is composed of the two noncoding roX (RNA on the X) RNAs and at least five proteins, including the RNA helicase Maleless (MLE). MLE contains two highly conserved double stranded RNA binding domains (DRBDs) at the N terminus. We investigated the roles of the roX RNAs and MLE helicase through experiments using classical genetic methods to generate and analyze the effects of mutants and mutant transgenes, immunolocalization experiments to study MSL protein and roX RNA to chromosomes. For the first time in vivo, we demonstrate that MLE associates with double stranded RNA in a sequence non-specific manner that is independent of other DCC components. Importantly, we find that the DSRBDs of MLE are essential for dosage compensation but are not required for MLE localization to the male X chromosome. We propose that although the DSRBDs are not essential for ds RNA binding, they may act synergistically with other domains of MLE or other MSLs to associate with RNA in vivo. We propose that a MLE/ roX RNA association involving secondary structure formed by the roX RNAs may be involved in the assembly, stabilization, or function of the DCC.</p>
dc.format.extent 1502842 bytes
dc.format.mimetype application/pdf
dc.language.iso en_US
dc.subject Biology, Genetics
dc.subject dosage compensation
dc.subject double stranded RNA binding domain
dc.subject Drosophila
dc.subject maleless
dc.subject MLE
dc.subject roX
dc.title Investigation of the roX RNAs and the RNA Helicase MLE in Dosage Compensation in Drosophila melanogaster
dc.type Dissertation
dc.department Molecular Genetics and Microbiology
duke.embargo.months 12 2010-05-18T05:00:39Z

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