The function and evolution of RNA editing in Drosophila
Abstract/Contents
- Abstract
- Many important modifications are used to tweak genomically-encoded information as it is being transcribed and translated. One type of RNA modification, adenosine-to-inosine (A-to-I) RNA editing, is a process in which the adenosine deaminase acting on RNA (ADAR) proteins catalyze the conversion of certain adenosines to inosines, which are treated by the cellular machinery as guanosines. A-to-I RNA editing is essential for the neurological and immune well-being of many animals, and it is a widespread process: There are thousands to millions of editing sites across the transcriptomes of flies and humans, respectively. However, it is largely unknown which sites are important, what their individual functions are, and what makes particular adenosines edited. In this dissertation, Drosophila is used as a model organism to explore key questions about the function and evolution of RNA editing, and the characteristics of RNA editing substrates. First, in Chapter 2, I describe the generation and characterization of an ADAR deaminase inactive point mutant fly and find that Drosophila ADAR has both neurological and immune RNA editing-dependent functions. Secondly, in Chapters 3 and 4, I explore the characteristics of edited RNA. I describe a computational pipeline used to predict the regulatory sequences base-paired to regions that undergo RNA editing and derive rules about RNA editing substrates, through an examination of the changes in RNA sequence and structure associated with changes in RNA editing across lines of Drosophila melanogaster (Chapter 3), and across Drosophila species (Chapter 4). Furthermore, a large fraction of nonsynonymous and noncoding editing events are evolutionarily constrained and therefore likely functionally important. Finally, in Chapter 5, I explore the functions of individual RNA editing events in vivo, through the generation and characterization of RNA editing event-specific mutants. These mutants validated some RNA structure predictions from Chapter 3. Furthermore, they do not have the severe phenotypes of the Adar mutants described in Chapter 2, suggesting that the editing events perturbed here could have subtle or redundant functions. Overall, this dissertation provides insights into the function and evolution of RNA editing events and their substrates.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Deng, Patricia | |
|---|---|---|
| Associated with | Stanford University, Department of Genetics. | |
| Primary advisor | Li, Jin | |
| Thesis advisor | Li, Jin | |
| Thesis advisor | Fire, Andrew Zachary | |
| Thesis advisor | Fraser, Hunter B | |
| Thesis advisor | Lipsick, Joseph Steven, 1955- | |
| Advisor | Fire, Andrew Zachary | |
| Advisor | Fraser, Hunter B | |
| Advisor | Lipsick, Joseph Steven, 1955- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Patricia Deng. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Patricia Hannah Deng
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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