RNA editing in the Rat brain

Adenosine-to-inosine (A-to-I) RNA editing is an epigenetic modification catalyzed by adenosine deaminases acting on RNA (ADARs), and is especially prevalent in the brain. Using microfluidics-based multiplex PCR sequencing (mmPCR-seq) to assess A-to-I editing at 146 pre-selected, conserved sites, we found that editing was generally higher in adult compared to neonatal rat brain, and that at birth, global editing was lower in prefrontal cortex than in amygdala. Prereproductive stress (PRS) affected editing at the serotonin receptor 2c, and editing at this site was significantly altered in offspring of PRS rats across two generations. Changes in ADAR expression did not correlate with editing changes induced by development or stress. Our findings indicate that mmPCR-seq can accurately detect RNA editing in rat brain samples, and confirm previous accounts of a developmental increase in RNA editing rates. Altered RNA editing rates in offspring of stress-exposed rats complements growing literature on the transgenerational effects of stress. We report the application of mmPCR-seq to the Rat brain and oocytes. We quantified RNA editing at 146 different loci in 85 samples from different groups (Age, tissue, stress) using a microfluidic multiplex PCR method coupled with deep sequencing.