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
Nature neuroscience · 2019 · Vol. 22 (1) · pp. 25-36
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.
Linked datasets 4
Widespread RNA editing dysregulation in Autism Spectrum Disorders [eCLIP-seq]
Homo sapiens
16 data files
| File | Type | Size |
|---|---|---|
| fix_FXR_In_D501_L000_R1_001.unassigned.barcoded.fastq.gz | RIP-Seq | 2.9 GB |
| fix_FXR_In_D502_701_L000_R1_001.unassigned.barcoded.fastq.gz | RIP-Seq | 3.3 GB |
| SRR6365478_GSM2883063 | RIP-Seq | 227.0 MB |
| SRR6365479_GSM2883064 | RIP-Seq | 2.9 GB |
| SRR6365480_GSM2883065 | RIP-Seq | 199.0 MB |
| SRR6365481_GSM2883066 | RIP-Seq | 3.3 GB |
| SRR6365482_GSM2883067 | RIP-Seq | 72.0 MB |
| SRR6365483_GSM2883068 | RIP-Seq | 566.0 MB |
| SRR6365484_GSM2883069 | RIP-Seq | 131.0 MB |
| SRR6365485_GSM2883070 | RIP-Seq | 551.0 MB |
| TBN_50_S37_L003_R1_001.unassigned.barcoded.fastq.gz | RIP-Seq | 566.8 MB |
| TBN_51.R1.fastq.gz | RIP-Seq | 72.2 MB |
| TBN_54_S41_L003_R1_001.unassigned.barcoded.fastq.gz | RIP-Seq | 551.5 MB |
| TBN_55.R1.fastq.gz | RIP-Seq | 131.5 MB |
| XiaoCollab1-5079_IP.R1.fastq.gz | RIP-Seq | 227.3 MB |
| XiaoCollab2-5352_IP.R1.fastq.gz | RIP-Seq | 199.7 MB |
Widespread RNA editing dysregulation in Autism Spectrum Disorders [RNA-Seq]
Homo sapiens
8 data files
| File | Type | Size |
|---|---|---|
| carrier_sample_5212.1.fastq.gz | RNA-Seq | 10.9 GB |
| carrier_sample_5529.1.fastq.gz | RNA-Seq | 11.3 GB |
| fragileX_sample_5319.1.fastq.gz | RNA-Seq | 12.2 GB |
| fragileX_sample_5746.1.fastq.gz | RNA-Seq | 10.8 GB |
| SRR6363414_GSM2882283 | RNA-Seq | 12.2 GB |
| SRR6363415_GSM2882284 | RNA-Seq | 10.8 GB |
| SRR6363416_GSM2882285 | RNA-Seq | 10.9 GB |
| SRR6363417_GSM2882286 | RNA-Seq | 11.3 GB |
Widespread RNA editing dysregulation in Autism Spectrum Disorders
Homo sapiens
Widespread RNA editing dysregulation in Autism Spectrum Disorders II
Homo sapiens
11 data files
| File | Type | Size |
|---|---|---|
| control_sample_103710XX.1.fastq | RNA-Seq | 3.1 GB |
| control_sample_103710XX.1.fastq | RNA-Seq | 3.1 GB |
| control_sample_UCD1407.1.fastq | RNA-Seq | 3.2 GB |
| control_sample_UCD1407.2.fastq | RNA-Seq | 3.2 GB |
| fragileX_sample_103108GP.1.fastq | RNA-Seq | 4.8 GB |
| fragileX_sample_103108GP.2.fastq | RNA-Seq | 4.8 GB |
| fragileX_sample_JS03.1.fastq | RNA-Seq | 3.9 GB |
| SRR7610662_GSM3308621 | RNA-Seq | 4.8 GB |
| SRR7610663_GSM3308622 | RNA-Seq | 3.9 GB |
| SRR7610664_GSM3308623 | RNA-Seq | 3.2 GB |
| SRR7610665_GSM3308624 | RNA-Seq | 3.1 GB |
Potentially related datasets 5
These accessions were text-mined from the PMC full text. They may be referenced for comparison, cited from other studies, or otherwise mentioned without being primary data for this paper.
| Accession | Source | Title |
|---|---|---|
| GSE51264 | GSE · GEO GEO ↗ | Conserved expression of lincRNA during human and macaque prefrontal cortex development and maturation |
| GSE59288 | GSE · GEO GEO ↗ | Disruption of human-specific synaptogenesis program in autism [RNA-seq] |
| GSE107895 | GSE · GEO GEO ↗ | Widespread RNA editing dysregulation in Autism Spectrum Disorders [eCLIP-seq] |
| GSE117776 | GSE · GEO GEO ↗ | Widespread RNA editing dysregulation in Autism Spectrum Disorders II |
| GSE107867 | GSE · GEO GEO ↗ | Widespread RNA editing dysregulation in Autism Spectrum Disorders [RNA-Seq] |
Analysis pipelines 6
| Pipeline | Assay | Steps | Dataset |
|---|---|---|---|
| GSE107867 RNA-seq Data Processing geo_data_processing | RNA-seq | 14 | GSE107867 |
| GSE107895 eCLIP Data Processing geo_data_processing | eCLIP | 32 | GSE107895 |
| GSE107896 Data Processing geo_data_processing | — | 14 | GSE107896 |
| GSE117776 RNA-seq Data Processing geo_data_processing | RNA-seq | 14 | GSE117776 |
| GSE51264 Data Processing geo_data_processing | — | 5 | GSE51264 |
| GSE59288 RNA-seq Data Processing geo_data_processing | RNA-seq | 3 | GSE59288 |
Funding 11 grants
| Grant | Funder |
|---|---|
| R01 HG004659 | NHGRI NIH HHS (United States) |
| R00 HG009530 | NHGRI NIH HHS (United States) |
| U19 MH107367 | NIMH NIH HHS (United States) |
| U01 HG009417 | NHGRI NIH HHS (United States) |
| K99 HG009530 | NHGRI NIH HHS (United States) |
| U54 HG007005 | NHGRI NIH HHS (United States) |
| R01 HG006264 | NHGRI NIH HHS (United States) |
| T32 HG002536 | NHGRI NIH HHS (United States) |
| R01 MH094681 | NIMH NIH HHS (United States) |
| R01 HD036071 | NICHD NIH HHS (United States) |
| F32 MH114620 | NIMH NIH HHS (United States) |