Widespread RNA editing dysregulation in brains from autistic individuals

Transcriptomic analyses of postmortem brains have begun to elucidate the molecular abnormalities in autism spectrum disorder (ASD). However, a crucial pathway involved in synaptic development, RNA editing, has not yet been studied on a genome-wide scale. Here, we profiled global patterns of adenosine-to-inosine (A-to-I) editing in a large cohort of post-mortem ASD brains. We observed a global bias for hypoediting in ASD brains, which was shared across brain regions and involved many synaptic genes. We show that the Fragile X proteins, FMRP and FXR1P, interact with ADAR proteins and modulate A-to-I editing. Furthermore, we observed convergent patterns of RNA editing alterations in ASD and Fragile X syndrome, establishing this as a molecular link between these related diseases. Our findings, which are corroborated across multiple datasets, including dup15q cases associated with intellectual disability, highlight RNA editing dysregulation in ASD and reveal novel mechanisms underlying this disorder.