Tissue and Sex‐Specific Changes in RNA Editing During Induced Acute Inflammation

Abstract

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. ADAR1 also plays a role in regulating innate immunity and 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 mice. We are interested in expanding RNA editing data to include female animals. Lipopolysaccharide (LPS) was used to induce 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 editing sites. Inflammation was verified in the LPS injected mice through qRT‐PCR of ADAR1 and inflammatory cytokines. Inflammation led to editing levels in male mice that were distinctly different than female mice. There was also a difference in editing between the heart and the brain. This indicates a complex system where RNA editing is regulated in a tissue‐specific and sex‐specific manner. The tissue and sex‐specific changes in editing may provide insight into a mechanism by which tissues adapt to inflammation in unique ways. Overall, this work will uncover information on how infection and inflammation alter the physiology of each organ in a manner unique to each sex.