RT Journal Article
SR Electronic
T1 Widespread RNA editing dysregulation in Autism Spectrum Disorders
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 446625
DO 10.1101/446625
A1 Stephen Tran
A1 Hyun-Ik Jun
A1 Jae Hoon Bahn
A1 Adel Azghadi
A1 Gokul Ramaswami
A1 Eric L. Van Nostrand
A1 Thai B. Nguyen
A1 Yun-Hua E. Hsiao
A1 Changhoon Lee
A1 Gabriel A. Pratt
A1 Gene W. Yeo
A1 Daniel H. Geschwind
A1 Xinshu Xiao
YR 2018
UL http://biorxiv.org/content/early/2018/10/17/446625.abstract
AB Autism spectrum disorder (ASD) is a genetically complex, clinically heterogeneous neurodevelopmental disease. Recently, our understanding of the molecular abnormalities in ASD has been 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 post-mortem ASD brains. Strikingly, we observed a global bias of hypo-editing in ASD brains, common to different brain regions and involving many genes with known neurobiological functions. Through genome-wide protein-RNA binding analyses and detailed molecular assays, 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, thus establishing RNA editing as a molecular link underlying these two highly related diseases. Our findings support a role for RNA editing dysregulation in ASD and highlight novel mechanisms for RNA editing regulation.