Date of Award

Spring 2025

Language

English

Embargo Period

4-30-2025

Document Type

Master's Thesis

Degree Name

Master of Science (MS)

College/School/Department

Department of Chemistry

Program

Chemistry

First Advisor

Alan Chen

Committee Members

Alan Chen, Michael Yeung, Sweta Vangaveti

Keywords

miRNA, miR-34a, mRNA, argonaute, AGO2, molecular dynamics simulations

Subject Categories

Computational Chemistry

Abstract

MicroRNAs (miRNA) are a class of small non-coding RNAs that play a key role in gene silencing. miRNAs form an RNA-induced silencing complex (RISC) with the argonaute 2 (AGO2) protein in order to control gene expression through silencing messenger RNAs (mRNA). The ability for a miRNA-mRNA complex to fit into AGO2 and form the RISC is based on the location and characteristics of a central bulge, but the mechanism and interactions that lead to a functional RISC remain unknown. Using available experimental data, we modeled the miR-34 and NOTCH1 duplex inside of AGO2 with only the seed region base paired. The resulting structure was then simulated in a series of all atom molecular dynamics (MD) simulations with distance restraints being applied to the base pairs after the central bulge to investigate how the supplemental and tail region of the miRNA moves from the P channel to the N channel to bind with the mRNA.

License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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