Date of Award

6-2021

Document Type

Restricted (Opt-Out)

Degree Name

Bachelor of Science

Department

Biochemistry

First Advisor

Colleen M. Connelly

Keywords

miRNA, Guanine Quadraplex, Fluorescence, Microarray

Abstract

MicroRNAs (miRNA) are a form of small non-coding RNA that downregulates protein translation. It does this through directly binding to messenger RNA targets in an RNA-induced silencing complex (RISC). The biogenesis of miRNAs relies on two cleavage events, one of which is the cleavage of precursor miRNA (pre-miRNA) by the enzyme Dicer. Dicer needs to recognize the two nucleotide 3’ overhang of the pre-miRNA when it is in the canonical stem-loop structure for it to cleave. However, recent studies have shown some pre-miRNAs can form non-canonical guanine-quadruplex (G4) structures. MiRNA-92b is a clinically important miRNA due to its upregulation in multiple types of cancer and association with an increased resistance to platinum-based chemotherapy. Recently, miRNA-92b has been identified to exist in an equilibrium of the stem-loop and G4 structures in its pre-miR-92b state. We have identified small organic compounds that selectively bind to the G4 forming pre-miR-92b through small molecule microarray analysis. These compounds are being analyzed for their ability to stabilize the G4 structure and alter the structural equilibrium of pre-miR-92b through biochemical and biophysical means. We are further developing a fluorescence-based assay to study the structural equilibrium in pre-miR-92b to better understand the role of the G4 in miRNA processing.

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Rights Statement

No Copyright - United States