Date of Degree

9-2020

Document Type

Dissertation

Degree Name

Ph.D.

Program

Biology

Advisor

Diana Bratu

Committee Members

Frida Kleiman

Mitchell Goldfarb

Amanda Norvell

Heather Cook

Subject Categories

Cell Biology | Developmental Biology | Molecular Genetics

Keywords

Drosophila melanogaster, oogenesis, mRNA, Post-transcriptional gene regulation, P-body

Abstract

D. melanogaster oogenesis serves as an excellent system to study the life of an mRNA. Tremendous work has been done to understand the numerous complex mechanisms of mRNA regulation, still there is still so much that is yet to be discovered. In this thesis, I present studies I carried out to address several aspects of oskar mRNA post-transcriptional regulation. Leading me to extend our current understanding of the carefully controlled regulation of oskar mRNA life cycle via a myriad of proteins. I found that a specific NPC component, Nup154 is necessary not only for its export from the nucleus, but also to recruit crucial factors to the oskar mRNP. I also uncovered that while two proteins, Bruno 1 and Cup, are constant companions of oskar mRNA, the role they play in oskar’s life is dictated by space and time. Furthermore, unexpectedly, I discovered that P-bodies are not only able to ensure that mRNAs are safely stored in a translationally repressed state, but they are able to protect mRNAs from degradation via RNAi. My findings paint an intertwined mechanism of post-transcriptional gene regulation during oogenesis, generating important insight into the processes that govern RNA biology and it opens new doors for future explorations. oskar mRNA was named after the little boy who decided never to grow up in Gunter Grass’s Tin Drum novel. I think that, if he had all the support oskar receives during D. melanogaster oogenesis, maybe he would have changed his mind, since as we know, it takes a village to raise a child (or oskar)...

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