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Title: The role of nonsense mediated mRNA decay in Drosophila development
Author: Avery, P. S.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2010
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Here I show that the so-called core components of NMD are not all essential genes, since flies that lack the function of Upf3 are viable, in contrast to flies that lack the function of Upf1 and Upf2. By removing the upf1 and upf2 maternal contribution during oogenesis, I demonstrate that Upf1 and Upf2 are required during embryogenesis, as was the case in mice and zebrafish, exemplifying the fly as a valuable NMD model system for vertebrates. In addition, upf1 and upf2­ mutant eggs exhibit a specific dorsal appendage phenotype, possibly the result of developmental perturbation. I have observed that upf1 and upf2, but not upf3, mutant cell clones are unable to grow, suggesting that upf1 and upf2 mutant cells do not proliferate and, in addition, undergo apoptosis. This supported the hypothesis that Upf1 and Upf2 have Upf3-independent functions that are essential for cell and organism viability, and that NMD is not required for the development of an organism. NMD target gene expression levels were analysed using qPCR. My results suggested that potential NMD targets can be separated into distinct groups depending on which NMD factors are most important for mediating their degradation. In adult flies, genes with known PTCs required Upf2 and Upf3, but not Smg1 for their full degradation by NMD, whereas targets with as yet unidentified NMD-inducing features were fully stabilised only in upf2 mutants. These results suggest that Smg1 is a weak inducer of the pathway, rather than a core component, and that Upf3 is only essential for NMD of specific target mRNAs. In embryos, Upf1 and Upf2 were essential for NMD whereas Smg1 and Upf3 had only moderate effects.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available