Genome-wide analysis of differential RNA editing in epilepsy
File(s)
Supporting information
Published version
Author(s)
Type
Journal Article
Abstract
The recoding of genetic information through RNA editing contributes to proteomic diversity, but the extent and significance of RNA editing in disease is poorly understood. In particular, few studies have investigated the relationship between RNA editing and disease at a genome-wide level. Here, we developed a framework for the genome-wide detection of RNA sites that are differentially edited in disease. Using RNA-sequencing data from 100 hippocampi from mice with epilepsy (pilocarpine–temporal lobe epilepsy model) and 100 healthy control hippocampi, we identified 256 RNA sites (overlapping with 87 genes) that were significantly differentially edited between epileptic cases and controls. The degree of differential RNA editing in epileptic mice correlated with frequency of seizures, and the set of genes differentially RNA-edited between case and control mice were enriched for functional terms highly relevant to epilepsy, including “neuron projection” and “seizures.” Genes with differential RNA editing were preferentially enriched for genes with a genetic association to epilepsy. Indeed, we found that they are significantly enriched for genes that harbor nonsynonymous de novo mutations in patients with epileptic encephalopathy and for common susceptibility variants associated with generalized epilepsy. These analyses reveal a functional convergence between genes that are differentially RNA-edited in acquired symptomatic epilepsy and those that contribute risk for genetic epilepsy. Taken together, our results suggest a potential role for RNA editing in the epileptic hippocampus in the occurrence and severity of epileptic seizures.
Date Issued
2017-05-01
Date Acceptance
2017-01-10
Citation
Genome Research, 2017, 27, pp.440-450
ISSN
1549-5469
Publisher
Cold Spring Harbor Laboratory Press
Start Page
440
End Page
450
Journal / Book Title
Genome Research
Volume
27
Copyright Statement
© 2017 Srivastava et al.; Published by Cold Spring Harbor Laboratory Press. This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/
Sponsor
Commission of the European Communities
Medical Research Council (MRC)
Medical Research Council (MRC)
UCB Biopharma SPRL
Imperial College Healthcare NHS Trust- BRC Funding
Grant Number
602102
MR/M004716/1
MR/N01121X/1
4400109351
RDA03
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Biotechnology & Applied Microbiology
Genetics & Heredity
DE-NOVO MUTATIONS
DNA-SEQUENCE DIFFERENCES
TEMPORAL-LOBE EPILEPSY
GENE SET ANALYSIS
HUMAN TRANSCRIPTOME
WIDESPREAD RNA
INTELLECTUAL DISABILITY
PILOCARPINE MODEL
MOUSE STRAINS
HUMAN CANCERS
Bioinformatics
06 Biological Sciences
11 Medical And Health Sciences
Publication Status
Published