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Analysis of Various Drosophila ADAR Isoforms and Their Dimerization

Kohram, Fatemeh
http://orcid.org/0000-0001-6679-3478
http://rave.ohiolink.edu/etdc/view?acc_num=miami1616716673416509

Abstract Details

2021, Doctor of Philosophy, Miami University, Cell, Molecular and Structural Biology (CMSB).
A-to-I RNA editing is one of the most abundant types of RNA editing found in various metazoans. Adenosine deaminases acting on RNA (ADAR) enzymes form dimers to catalyze the A-to-I editing mechanism on double-strand RNAs, resulting in changes in downstream mechanisms of the edited RNA. Altered RNA editing has been found in various human diseases such as cancers, immune system dysfunctions, and neurological disorders, thus making ADARs and A-to-I editing potential markers to target these diseases. This dissertation describes analyzing the formation of heterodimers between various Drosophila melanogaster ADAR isoforms, to elucidate the possibility of each isoform to participate in the A-to-I editing mechanism through dimer formation. Furthermore, by deletion of N-terminal and C-terminal ADAR domains, we have investigated the significance of these structures in ADAR dimerization. In Drosophila melanogaster, two major classes of ADAR isoforms are transcribed from a single ADAR gene where full-length (FL) isoforms possess a deaminase domain and thus can potentially catalyze A-to-I editing, while the truncated (TR) isoforms do not have the deaminase domain. Both FL and TR isoforms are found in fly embryos where A-to-I editing is significantly low. This suggests a possible mechanism for the TR isoform in controlling FL ADAR isoform function by forming heterodimers or competing for the same substrates. We have investigated dimer formations between FL and TR isoforms, as the demonstration of such dimer formations is the first step to understanding the function of TR isoforms. We have analyzed various dimer formations using the yeast two-hybrid method and measuring the binding affinity of each dimer via a-Gal assay. Furthermore, one of the FL ADAR isoforms (the F3/4-M2 isoform) found in Drosophila melanogaster is translated starting from a downstream methionine compared to the known fully functional FL isoform (F3/4). We have compared the dimerization of F3/4-M2 to F3/4 to study the importance of the missing amino acids on the N-terminal region of F3/4-M2 in dimerization. We have also tested the dimerization of various other isoforms lacking the N-terminal region and parts of the deaminase domain to investigate their significance in dimerization.
Paul James (Advisor)
Carol Dabney-Smith (Advisor)
Joyce Fernandes (Committee Member)
Susan Hoffman (Committee Member)
Chun Liang (Committee Member)
78 p.
Molecular Biology
Drosophila; ADAR; RNA editing

Recommended Citations

Citations

  • Kohram, F. (2021). Analysis of Various Drosophila ADAR Isoforms and Their Dimerization [Doctoral dissertation, Miami University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=miami1616716673416509

    APA Style (7th edition)

  • Kohram, Fatemeh. Analysis of Various Drosophila ADAR Isoforms and Their Dimerization. 2021. Miami University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=miami1616716673416509.

    MLA Style (8th edition)

  • Kohram, Fatemeh. "Analysis of Various Drosophila ADAR Isoforms and Their Dimerization." Doctoral dissertation, Miami University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=miami1616716673416509

    Chicago Manual of Style (17th edition)

miami1616716673416509
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This open access ETD is published by Miami University and OhioLINK.