Landscape of A-I RNA editing in mouse, pig, macaque, and human brains

Adenosine-to-inosine (A-I) RNA editing is one of the most abundant post-transcriptional RNA modification processes. However, the roles of A-I RNA editing in the evolution and functions of primate brains are underexplored. Here, we perform whole-genome and whole-transcriptome sequencing of 39 anatomically defined brain regions of adult Macaca fascicularis and identify 2 782 079 A-I editing sites, including 2009 recoding sites enriched in genes related to neurotransmission functions. Most of macaque brain A-I editing sites are detected in the cerebral cortex, cerebellum, and amygdala. The brain A-I editing activity is associated with the estimated proportion of neurons to some extent. Comparison of A-I editing in mouse, pig, macaque, and human brains reveals that primates exhibit higher editing levels, specifically enriched in genes encoding neurotransmitter receptors. We identify 478 598 conserved brain editing sites between human and macaque brains, mostly found in the cerebral cortex and enriched in genes related to the cytoskeletal system and ubiquitin-dependent protein degradation pathway. Our study sheds light on the importance of post-transcriptional A-I RNA editing in the evolution and function of nervous systems.