Regulation of a Messenger: Raising \u3ci\u3eoskar\u3c/i\u3e, It Takes a Village

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)..

The temporally controlled expression of Drongo, the fruit fly homolog of AGFG1, is achieved in female germline cells via P-bodies and its localization requires functional Rab11

<p>To achieve proper RNA transport and localization, RNA viruses exploit cellular vesicular trafficking pathways. AGFG1, a host protein essential for HIV-1 and Influenza A replication, has been shown to mediate release of intron-containing viral RNAs from the perinuclear region. It is still unknown what its precise role in this release is, or whether AGFG1 also participates in cytoplasmic transport. We report for the first time the expression patterns during oogenesis for Drongo, the fruit fly homolog of AGFG1. We find that temporally controlled Drongo expression is achieved by translational repression of <i>drongo</i> mRNA within P-bodies. Here we show a first link between the recycling endosome pathway and Drongo, and find that proper Drongo localization at the oocyte's cortex during mid-oogenesis requires functional Rab11.</p

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

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