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Title: Elucidating the mechanism of mRNA translation during Drosophila oogenesis
Author: Davidson, Alexander
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2015
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mRNA localisation and translational control is a conserved, universal process involved in a number of essential cellular processes. Localised mRNAs are processed throughout their life cycle from transcription to degradation. How and where key mRNA remodelling steps occur is unclear. Furthermore, how mRNAs are translationally repressed during their transport, but translationally activated once localised, is a key question in the field. The Drosophila oocyte is a well used model system, and is patterned by the differential localisation of gurken, bicoid, oskar and nanos, which are all transcribed in the nuclei of the adjacent supporting nurse cell tissue. Here, I image localised mRNAs in live nurse cells and detect gurken with single molecule fluorescent in-situ hybridisation techniques for the first time. I use these assays to characterise the properties of gurken and oskar mRNAs in the nurse cells, and show they are strikingly different to the oocyte. I find that Processing bodies, which are key sites of translational regulation in the oocyte, contain significantly lower levels of the translational activator and Drosophila CPEB homolog, Orb. I show that, in contrast to oskar, whose translation is prevented during transport mainly by repressor proteins, gurken mRNA translation in the nurse cells is not prevented by a single repressor, but rather the absence of its translational activator, Orb/CPEB, in this tissue. Ectopic expression of Orb in the nurse cells is sufficient for the association of gurken with Processing bodies and premature gurken translation. These data highlight a new model for translational regulation through restricted spatial access to a translational activator, and I propose that such a mechanism could be widely deployed in other tissues.
Supervisor: Davis, Ilan Sponsor: Wellcome Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available