Date of Graduation

Spring 2022

Degree

Master of Science in Cell and Molecular Biology

Department

Biomedical Sciences

Committee Chair

Randi Ulbricht

Abstract

A-to-I RNA editing is a process where select adenosine (A) nucleotides are deaminated by an editing enzyme, ADAR, to become inosines (I) in RNA transcripts. RNA editing can affect the sequence of the encoded protein and the regulation of the RNA. ADAR1 also plays a role in regulating innate immunity and its expression is upregulated during inflammation. Current data on the effects of increasing ADAR1 on RNA editing is limited, and most studies are completed only in male animals. We are interested in expanding RNA editing data to include female animals. Lipopolysaccharide (LPS) was used to induce acute inflammation and increase ADAR1. Organs were dissected four hours after LPS injection and RT-PCR was used to amplify regions around editing sites of known targets. The amplicons were sequenced and analyzed by measuring the amount of nonedited nucleotides and edited nucleotides at select sites. Inflammation did not affect levels of RNA editing in the heart or brain. There was also no significant difference in editing between males and females in the heart or brain. However, our analysis did reveal sex- and inflammation-dependent editing in the skeletal muscle. This indicates that the level of RNA editing is independently regulated in each tissue. The process by which sex-dependent editing might occur in the skeletal muscle but not in other tissues is currently unknown. Overall, this work helps us understand how the effects of infection and inflammation are regulated to minimize damage and unwanted physiological consequences.

Keywords

RNA editing, FLNA, ADAR, sex-specific, tissue-specific, acute inflammation

Subject Categories

Biochemistry | Cell Biology | Molecular Biology

Copyright

© Claire E. Nichols

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