Degree Type

Creative Component

Semester of Graduation

Spring 2020

Department

Biomedical Sciences

First Major Professor

Anumantha Kanthasamy

Degree(s)

Master of Science (MS)

Major(s)

Biomedical Sciences

Abstract

One of the most well characterized RNA modifications is the addition of a methyl group to the amine nitrogen of adenosine nucleotides. This methylation, named N6-methyladenoside (m6A), is known to affect the stability of mRNA. YTHDF2 is a reader protein responsible for recognition and degradation of transcripts containing m6A methylation. Previous work in our lab has shown that levels of YTHDF2 are decreased in astrocytes following exposure to manganese. Manganese exposure causes oxidative stress in the cell and is known to cause a disease called manganism, which has many similarities to Parkinson’s disease. The neurotoxicity of manganese may also be affecting the levels of YTHDF2 and related proteins in neurons. The purpose of this project was to see if manganese exposure also affects YTHDF2 levels in neurons, and further determine the role of YTHDF2 in response to a stimulus like manganese. Mn9D neuronal cells were subjected to 24 hour treatments with 300μM of manganese. Western blot analysis revealed a decrease in YTHDF2 protein expression compared to a control. qRT-PCR also showed a decrease in the mRNA of YTHDF2 as well as two other m6A associated proteins METTL3 and FTO. Taken together with results from previous studies, this project demonstrates that manganese exposure causes a decrease in YTHDF2 indicating it may be involved in the cellular response to neurotoxicity, and oxidative stress and may be impacted by prosurvival pathways.

Copyright Owner

Huffman, Elliana

File Format

PDF

Embargo Period (admin only)

5-1-2022

1

Available for download on Sunday, May 01, 2022

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