1. Widespread RNA editing dysregulation in brains from autistic individuals
- Author
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Tran, Stephen S, Jun, Hyun-Ik, Bahn, Jae Hoon, Azghadi, Adel, Ramaswami, Gokul, Van Nostrand, Eric L, Nguyen, Thai B, Hsiao, Yun-Hua E, Lee, Changhoon, Pratt, Gabriel A, Martínez-Cerdeño, Verónica, Hagerman, Randi J, Yeo, Gene W, Geschwind, Daniel H, and Xiao, Xinshu
- Subjects
Biological Psychology ,Psychology ,Fragile X Syndrome ,Rare Diseases ,Autism ,Pediatric ,Genetics ,Human Genome ,Neurosciences ,Intellectual and Developmental Disabilities (IDD) ,Brain Disorders ,Mental Health ,1.1 Normal biological development and functioning ,2.1 Biological and endogenous factors ,Mental health ,Neurological ,Adenosine Deaminase ,Autistic Disorder ,Brain ,Fragile X Mental Retardation Protein ,Gene Expression Profiling ,Humans ,Neurons ,RNA Editing ,RNA-Binding Proteins ,Cognitive Sciences ,Neurology & Neurosurgery ,Biological psychology - Abstract
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.
- Published
- 2019