Deciphering the regulation of A-to-I RNA editing in the Drosophila brain
Abstract/Contents
- Abstract
- RNA editing increases genetic diversity by altering RNA sequences from those encoded by the genome. The most prevalent type of RNA editing is adenosine-to-inosine (A-to-I) RNA editing, where the Adenosine Deaminase Acting on RNA (ADAR) protein family converts adenosines into inosines, which are then recognized as guanosines by the cellular machinery. ADAR enzymes are conserved in numerous species including Drosophila, where dADAR edits over 5,000 sites at widely varying frequency, creating different ratios of modified transcripts. These editing events are necessary for proper neuronal function of the fly; however, the regulation of editing levels at particular editing sites is poorly understood. This thesis addresses the two primary modes of regulation of RNA editing in Drosophila, cis and trans regulation. Chapter 1 provides an introduction to ADAR editing, the regulatory role of both the cis determinants and the trans factors that influence editing levels, and the function of RNA editing in the brain. In Chapter 2, I evaluate RNA editing level differences between different neuronal cell types in the fly brain, uncovering the extent to which RNA editing is differentially regulated in different cell types. Next, in Chapter 3, I analyze how both cis and trans regulatory factors contribute to RNA editing differences between two closely related fly species, D. melanogaster and D. sechellia, highlighting the critical role of cis sequence changes in altering RNA structural stability around editing sites. Finally, in Chapter 4, I discuss the novel and evolutionarily conserved role of the RNA binding protein Zinc-finger protein at 72D (Zn72D) as an ADAR-interacting protein and regulator of RNA editing. Together, these chapters provide insight into the variability of editing levels within the brain and the cis and trans regulatory factors that influence these editing events, improving our understanding of this critical co-transcriptional process.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2018 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Sapiro, Anne |
|---|---|
| Associated with | Stanford University, Department of Genetics. |
| Primary advisor | Li, Jin |
| Thesis advisor | Li, Jin |
| Thesis advisor | Clandinin, Thomas R. (Thomas Robert), 1970- |
| Thesis advisor | Fire, Andrew Zachary |
| Thesis advisor | Gitler, Aaron D |
| Advisor | Clandinin, Thomas R. (Thomas Robert), 1970- |
| Advisor | Fire, Andrew Zachary |
| Advisor | Gitler, Aaron D |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Anne Sapiro. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2018. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2018 by Anne La Fleur Sapiro
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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