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

doi:10.1038/s41593-018-0287-x

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 journal › Article › peer-review

116 Scopus citations

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.

Original language	English (US)
Pages (from-to)	25-36
Number of pages	12
Journal	Nature neuroscience
Volume	22
Issue number	1
DOIs	https://doi.org/10.1038/s41593-018-0287-x
State	Published - Jan 1 2019
Externally published	Yes

ASJC Scopus subject areas

General Neuroscience

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Tran, S. S., Jun, H. I., Bahn, J. H., Azghadi, A., Ramaswami, G., Van Nostrand, E. L., Nguyen, T. B., Hsiao, Y. H. E., Lee, C., Pratt, G. A., Martínez-Cerdeño, V., Hagerman, R. J., Yeo, G. W., Geschwind, D. H., & Xiao, X. (2019). Widespread RNA editing dysregulation in brains from autistic individuals. Nature neuroscience, 22(1), 25-36. https://doi.org/10.1038/s41593-018-0287-x

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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.",

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AU - Geschwind, Daniel H.

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Widespread RNA editing dysregulation in brains from autistic individuals

Abstract

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