ADAR2 affects mRNA coding sequence edits with only modest effects on gene expression or splicing in vivo

Adenosine deaminases bind double stranded RNA and convert adenosine to inosine. Editing creates multiple isoforms of neurotransmitter receptors, such as with <i>Gria2</i>. <i>Adar2</i> KO mice die of seizures shortly after birth, but if the <i>Gria2</i> Q/R editing site is mutated to mimic the edited version then the animals are viable. We performed RNA-Seq on frontal cortices of <i>Adar2</i>^−/−<i>Gria2</i>^R/Rmice and littermates. We found 56 editing sites with significantly diminished editing levels in <i>Adar2</i> deficient animals with the majority in coding regions. Only two genes and three exons showed statistically significant differences in expression levels. This work illustrates that ADAR2 is important in site-specific changes of protein coding sequences but has relatively modest effects on gene expression and splicing in the adult mouse frontal cortex.