GSE107895 Widespread RNA editing dysregulation in Autism Spectrum Disorders [eCLIP-seq]

Contributors : Stephen Tran ; Hyun-Ik Jun ; Jae H Bahn ; Adel Azghadi ; Gokul Ramaswami ; Eric Van Nostrand ; Thai Nguyen ; Yun-Hua E Hsiao ; Chang H Lee ; Gabriel Pratt ; Gene W Yeo ; Daniel H Geschwind ; Xinshu XiaoSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensAutism spectrum disorder (ASD) is a neurodevelopmental disease with complex heterogeneity and aberrations in multiple levels of neurobiology. Recently, our understanding of the molecular abnormalities in ASD has been greatly expanded through transcriptomic analyses of postmortem brains. However, a crucial molecular pathway involved in synaptic development, RNA editing, has not yet been studied on a genome-wide scale. Here we profiled the global patterns of adenosine-to-inosine (A-to-I) editing in a large cohort of ASD cortices and cerebella. Strikingly, we observed a global bias of hypoediting in ASD brains, common to different brain regions and involving many genes with critical neurological function. The large-scale RNA editing changes allowed us to reveal novel insights of RNA editing regulation. Through genome-wide protein-RNA binding analyses and detailed molecular assays, we show that the Fragile X proteins, FMRP and FXR1P, interact with ADAR protens and modulate A-to-I editing. Furthermore, we observed convergent patterns of RNA editing alterations between ASD and Fragile X syndrome, thus establishing RNA editing as a novel molecular link underlying these two hig...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research