Description
- Abstract:
- A-to-I RNA editing is the post-transcriptional modification of pre-mRNA transcripts,where specific adenosine residues are converted to inosine by Adenosine DeaminasesActing on RNA (ADARs). This modification can result in amino acid substitutions thatchange the primary protein structure and increase the diversity of protein productsoriginating from a single gene. In Drosophila melanogaster, many genes that undergo A-to-I editing are enriched in the nervous system. Transcripts encoding voltage-gatedpotassium channels from Shaker, Shab, and ether-a-go-go (eag) genes undergo A-to-Iediting events that to introduce amino acid substitutions in highly conserved residueswithin functionally important regions of the channel. Examination of editing in thesegenes revealed conservation of these editing events across multiple Drosophila species aswell as spatial and temporal regulation of RNA editing. Electrophysiology studies ofdifferentially edited isoforms of Shaker and Shab channels demonstrate that editingaffects gating kinetics and inactivation properties for these channels. Furthermore,comparative genomics was employed to identify the ECS (editing site complementarysequences) elements, which are the cis-regulatory elements directing editing of thesesites. Mutations introduced into these ECS elements, or in the editing sites themselves,by homologous recombination in Drosophila disrupt editing events in vivo. Lastly, thismethod was also employed to introduce the human disease allele for chronicneuromyotonia in the Shaker locus of Drosophila. In addition to conferring somerelevant human disease features within these flies, this mutation uncovers a novel role ofShaker-mediated excitability in the modulation of aggressive behaviors and courtshipbehavioral defects. These mutants provide a system in which the specific contributionsof KV channel editing can be examined in the generation of fly behavior and propernervous system functioning as well as the in vivo role of K+ channel pathology withinDrosophila.
- Notes:
- Thesis (Ph.D. -- Brown University (2011)
Access Conditions
- Rights
- In Copyright
- Restrictions on Use
- Collection is open for research.
Citation
Maloney, Rachel A.,
"A-to-I RNA Editing of Voltage-Gated Potassium Channels: Regulation and Functional Consequences in Drosophila melanogaster."
(2011).
Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.7301/Z03R0R4G
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Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations
Theses and Dissertations for the Molecular Biology, Cell Biology, and Biochemistry department....