Date of Award

6-2022

Document Type

Restricted (Opt-Out)

Degree Name

Bachelor of Science

Department

Biology

First Advisor

Steven Rice

Second Advisor

Colleen Connelly

Keywords

microRNA, small molecule, RNA structure, cancer

Abstract

Under the broad classification of RNA, there is a family of RNAs called microRNAs. MicroRNAs (miRNAs) are noncoding RNAs that act as post-transcriptional gene regulators. MiRNAs are transcribed from the genome into large stem-loop structures known as primary miRNAs (pri-miRNAs). In the nucleus, pri-miRNAs are processed by two main enzymes into shorter stem loop precursors or pre-miRNAs. Another enzyme, Dicer, is able to recognize and cleave the stem loop structure of pre-miRNAs to produce the mature miRNAs, which then go on to regulate protein expression. In some cases, pre-miRNAs can fold into an alternative conformation known as a G-quadruplex. Dicer is unable to cleave the G-quadruplex conformation of these pre-miRNA. Without the formation of mature miRNA, this strand cannot go on to regulate protein expression. The misregulation of certain miRNAs with stem loop and G-quadruplex conformations have been identified in the formation of cancer cells, as the mature miRNA can lead to the downregulation of tumor suppressant proteins. To explore the role this alternative structure plays in miRNA regulation, we have identified small organic molecules that bind to the G-quadruplex conformation of pre-let-7e. If the small molecules stabilize the G-quadruplex, miRNA maturation could be inhibited, leading to a downregulation of the let-7e target proteins. These compounds were identified for their selective binding to a fluorescently labeled pre-let-7e RNA through a technique known as small molecule microarray screening. Through fluorescence titrations, we have identified molecules that bind to the pre-let-7e RNA in a dose-dependent fashion.

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In Copyright - Educational Use Permitted.