ORCID

https://orcid.org/0000-0002-7924-0052

Date of Award

12-18-2024

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Molecular Cell Biology)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

The regulation of messenger RNA (mRNA) splicing, stability, and translation efficiency are major modes for controlling gene expression – which is essential for life. RNA-binding proteins (RBPs) and microRNAs (miRNAs) are trans-acting factors that bind to cis-elements influencing the stability and translation of the mRNA transcript. AU-rich elements (AREs) are cis-elements that are targeted by AU-rich element binding proteins (ARE-BPs). Here, I show a novel role for AREs and AU-rich element binding protein 1 (AUF1) during alternative splicing and report on interactions of RBPs and miRNAs to design a new treatment for breast cancer by interrupting these interactions in the 3’UTR. Using a reporter-based approach we show that AREs can impact splice-site selection based on their location in the 3’UTR. Using CRISPR engineered AUF1 hypomorph and AUF1 isoform add-back cell lines we show AUF1 and AREs impact alternative splicing endogenously, and that AUF1 isoforms regulate RNA at different levels. Additionally, through our knowledge of miRNA and AUF1 interactions, we design antisense oligos (ASOs) to target motifs in the 3’UTR of BRCA1 to rescue BRCA1 haploinsufficiency.

Language

English (en)

Chair and Committee

Sergej Djuranovic

Committee Members

Andrew Yoo; Hani Zaher; Joseph Dougherty; Kristen Kroll

Available for download on Tuesday, January 13, 2026

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