Date of Graduation

Summer 2023

Degree

Master of Science in Cell and Molecular Biology

Department

Biomedical Sciences

Committee Chair

Randi Ulbricht

Abstract

Inflammation occurs as a result of insult or infection within the body. Individual cells respond to inflammation by upregulating genes that help mediate the immune response, such as ADAR1. ADAR1 helps regulate the immune response but also catalyzes a process called RNA editing. RNA editing alters the sequence of select mRNAs to alter the encoded proteins. The result is altered function of the encoded protein, which is often beneficial for the cell. Our goal was to determine how inflammation affects the function of ADAR1. Since we know that the effects of inflammation vary between different organs and sexes, we examined ADAR1 function in heart, brain, and muscle in male and female mice after the introduction of LPS, an inflammation-inducing agent. We found that editing in the heart and brain was unaffected. However, RNA editing of FLNB in skeletal muscle was increased by LPS in males but was unaffected in females. Another RNA editing target, FLNA was unaffected by the treatment of LPS, but showed a sex-dependent difference in editing. These results show that the effects of inflammation may selectively affect the function of FLNB in muscle. Furthermore, expression of inflammatory factors ADAR1, TNFα, and MDA5 was induced by LPS, as expected, but TNFα and MDA5 expression was induced more in females. Our work suggests that the impact of sex on inflammatory factors may also indirectly affect the rate of RNA editing of select transcripts in select tissues.

Keywords

RNA editing, ADAR, FLNA, FLNB, MDA5, TNFα, sex-specific, tissue-specific, acute inflammation

Subject Categories

Biology | Immunity | Molecular Biology

Copyright

© Kelsey R. Kendrick

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