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Title page for ETD etd-03252006-110338


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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