Widespread RNA editing dysregulation in brains from autistic individuals.
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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Linked Datasets (4)
Widespread RNA editing dysregulation in Autism Spectrum Disorders [eCLIP-seq]
Homo sapiens8 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 |
| 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 sapiens4 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 |
Widespread RNA editing dysregulation in Autism Spectrum Disorders
Homo sapiensWidespread RNA editing dysregulation in Autism Spectrum Disorders II
Homo sapiens7 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 |
Potentially Related Datasets (2)
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.
Conserved expression of lincRNA during human and macaque prefrontal cortex development and maturation