Circadian A-to-I RNA editing in the central nervous system
The transcription-translation feedback loop formed by core clock genes regulates the circadian transcription of thousands of genes. Interestingly, approximately 70% of rhythmic mRNAs are not rhythmically transcribed, implicating circadian post-transcriptional mechanisms in the generation of mRNA oscillations. While the interrelationship between circadian clocks and post-transcriptional events such as RNA splicing and degradation has long been appreciated, emerging evidence highlights the significance of ribonucleoside modifications in circadian biology. A recent study showed circadian expression and catalytic activity of the adenosine-to-inosine (A-to-I) RNA editing enzyme known as adenosine deaminase acting on RNA type 2 (ADAR2) in mouse liver. Though ADAR2 expression and A-to-I editing is most abundant in the brain, circadian A-to-I editing in the central nervous system has not been investigated. Here, we used a combination of qRT-PCR and Sanger sequencing to understand ADAR2-mediated editing rhythms of RNAs isolated from mouse brain. The results from this study will not only expand the role of A-to-I editing in circadian physiology, but will also inform the design and analysis of future studies of RNA editing. Results from this study will have implications on the ways A-to-I editing analyses are performed in future studies.