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.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-03252006-110338 |
| Date | 04 April 2006 |
| Creators | Xu, Ming |
| Contributors | Randy D. Blakely, P. Jeffrey Conn, David W. Piston, Alfred L. George, Jr., Ronald B. Emeson |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-03252006-110338/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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