Abstract 2015 Tissue and Sex-Specific RNA Editing During Induced Acute Inflammation

A-to-I RNA editing is a process where adenosine (A) nucleotides are deaminated by an editing enzyme, ADAR1, to become inosines (I) in select RNA transcripts. RNA editing can affect the sequence of the encoded protein as well as the regulation of the RNA. ADAR1p150 isoform also plays a role in regulating innate immunity and its expression is upregulated during inflammation, while ADAR2's expression is not influenced by inflammation. ADAR1 and ADAR2 have both overlapping and distinct RNA editing targets. We induced the p150 isoform of ADAR1 by injecting mice with lipopolysaccharide (LPS) and then measured the amount of RNA editing from peripheral organs such as heart and muscle, as well brain. The increased levels of ADAR1p150 that occurred after LPS injection did not affect levels of RNA editing in the heart or brain, however, we detected slight alteration of FLNB editing levels in muscle only. Our review of the literature noticed that RNA editing analysis was almost exclusively performed in male mice. We included female mice in our analysis and saw no significant difference in editing between males and females in the heart and brain, however, there are significant sex-dependent differences in editing in muscle. We also noticed that proinflammatory mediators MDA5 and TNFa were induced more in females than males. This indicates a complex system where RNA editing of each target is regulated independently by the compounding effects of tissue and sex. This study provides insight into how inflammation may alter the physiology of each tissue in each sex in a unique manner. This research is funded my Missouri State University, Biomedical Sciences