Widespread RNA editing dysregulation in brains from autistic individuals

Stephen S. Tran, Hyun Ik Jun, Jae Hoon Bahn, Adel Azghadi, Gokul Ramaswami, Eric L. Van Nostrand, Thai B. Nguyen, Yun Hua E. Hsiao, Changhoon Lee, Gabriel A. Pratt, Verónica Martínez-Cerdeño, Randi J. Hagerman, Gene W. Yeo, Daniel H. Geschwind, Xinshu Xiao

Research output: Contribution to journalArticlepeer-review

107 Scopus citations


Transcriptomic analyses of postmortem brains have begun to elucidate 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 postmortem brains of people with ASD. 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 RNA-editing enzymes (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 data sets, including dup15q (genomic duplication of 15q11.2-13.1) cases associated with intellectual disability, highlight RNA-editing dysregulation in ASD and reveal new mechanisms underlying this disorder.

Original languageEnglish
Pages (from-to)25-36
Number of pages12
JournalNature Neuroscience
Issue number1
StatePublished - 1 Jan 2019
Externally publishedYes


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