| Type of Document |
Dissertation |
| Author |
Xu, Ming
|
| Author's Email Address |
ming.xu@vanderbilt.edu |
| URN |
etd-03252006-110338 |
| Title |
MOLECULAR MECHANISMS OF ADAR2 LOCALIZATION AND SUBSTRATE SPECIFICITY |
| Degree |
PhD |
| Department |
Pharmacology |
| Advisory Committee |
| Advisor Name |
Title |
| Alfred L. George, Jr. |
Committee Chair |
| David W. Piston |
Committee Member |
| P. Jeffrey Conn |
Committee Member |
| Randy D. Blakely |
Committee Member |
| Ronald B. Emeson |
Committee Member |
|
| Keywords |
- RNA editing
- nucleolar localization
- specific recognition
- dsRNA
- Double-stranded RNA
- Adenosine deaminase
|
| Date of Defense |
2006-03-22 |
| Availability |
unrestricted |
Abstract
ADAR2-mediated adenosine-to-inosine (A-to-I) RNA editing can affect the coding potential, splicing pattern, stability, and localization of the targeted RNA transcripts. ADAR2 contains two double-stranded RNA binding motifs (dsRBM) and a conserved adenosine deaminase domain. To investigate how the dsRBMs of ADAR2 bind to natural substrates, we developed an NMR-based model of the complex formed between the two dsRBMs and an RNA duplex derived from a naturally-occurring ADAR2 substrate. These structural studies demonstrated that dsRBMs recognize specific structural determinants and hence contribute to substrate specificity. In addition, we demonstrated that the dsRBMs of ADAR2 differ in their ability to modulate subnuclear localization and editing activity although their sequences/structures are highly conserved, emphasizing the functional inequality between members of this conserved protein motif family.
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| Files |
| Filename |
Size |
Approximate Download Time
(Hours:Minutes:Seconds)
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| 28.8 Modem |
56K Modem |
ISDN (64 Kb) |
ISDN (128 Kb) |
Higher-speed Access |
| |
thesis.pdf |
9.41 Mb |
00:43:34 |
00:22:24 |
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