Defense Date

11-20-2020

Graduation Date

Fall 12-18-2020

Availability

One-year Embargo

Submission Type

dissertation

Degree Name

PhD

Department

Chemistry and Biochemistry

Committee Chair

Mihaela Rita Mihailescu

Committee Member

David W. Seybert

Committee Member

Michael Cascio

Committee Member

Bruce Armitage

Keywords

Alzheimer's disease, FMRP, FUS, microRNA, RNA structure, SARS-CoV-2

Abstract

The studies outlined in this dissertation encompass a broad focus, relating to the pathogenesis of neurological disorders such as Alzheimer’s disease, fragile X syndrome, and amyotrophic lateral sclerosis, as well as a novel infectious disease, COVID-19. However, all four studies detailed within this dissertation contain similar elements, namely, the coordinated role of RNA structure and function in essential molecular mechanisms. The results of these investigations allow us to speculate on various disease- related mechanisms, including dysregulated microRNA processing pathways, nucleocytoplasmic shuttling via distinct RNA-protein interactions, and fine-tuned molecular switches controlling genomic dimerization and viral hijacking of host cellular microRNAs. Taken together, these studies highlight the importance of RNA structure and function in relation to disease etiology and elucidate previously unknown molecular mechanisms to potentially be targeted by future therapeutic drug intervention.

Language

English

Additional Citations

Imperatore, J. A., Then, M. L., McDougal, K. B., & Mihailescu, M. R. (2020a). Characterization of a G-Quadruplex structure in pre-miRNA-1229 and in its Alzheimer’s disease-associated variant rs2291418: Implications for miRNA-1229 maturation. International Journal of Molecular Sciences, 21. https://doi.org/10.3390/ijms21030767

Imperatore, J. A., McAninch, D. S., Valdez-Sinon, A. N., Bassell, G. J., & Mihailescu, M. R. (2020b). FUS Recognizes G Quadruplex Structures Within Neuronal mRNAs. Frontiers in Molecular Biosciences, 7. https://doi.org/10.3389/fmolb.2020.00006

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