Genetic Control of RNA Editing in Neurodegenerative Disease

Authors

Sijia Wu
Qiuping Xue
Mengyuan Yang
Yanfei Wang
Pora Kim
Xiaobo Zhou
Liyu Huang

Publication Date

3-19-2023

Journal

Briefings in Bioinformatics

Abstract

A-to-I RNA editing diversifies human transcriptome to confer its functional effects on the downstream genes or regulations, potentially involving in neurodegenerative pathogenesis. Its variabilities are attributed to multiple regulators, including the key factor of genetic variants. To comprehensively investigate the potentials of neurodegenerative disease-susceptibility variants from the view of A-to-I RNA editing, we analyzed matched genetic and transcriptomic data of 1596 samples across nine brain tissues and whole blood from two large consortiums, Accelerating Medicines Partnership-Alzheimer's Disease and Parkinson's Progression Markers Initiative. The large-scale and genome-wide identification of 95 198 RNA editing quantitative trait loci revealed the preferred genetic effects on adjacent editing events. Furthermore, to explore the underlying mechanisms of the genetic controls of A-to-I RNA editing, several top RNA-binding proteins were pointed out, such as EIF4A3, U2AF2, NOP58, FBL, NOP56 and DHX9, since their regulations on multiple RNA-editing events were probably interfered by these genetic variants. Moreover, these variants may also contribute to the variability of other molecular phenotypes associated with RNA editing, including the functions of 3 proteins, expressions of 277 genes and splicing of 449 events. All the analyses results shown in NeuroEdQTL (https://relab.xidian.edu.cn/NeuroEdQTL/) constituted a unique resource for the understanding of neurodegenerative pathogenesis from genotypes to phenotypes related to A-to-I RNA editing.

Keywords

Humans, Neurodegenerative Diseases, RNA Editing, Transcriptome, Gene Expression Profiling, Quantitative Trait Loci, Eukaryotic Initiation Factor-4A, DEAD-box RNA Helicases, A-to-I RNA editing, RNA editing quantitative trait loci, neurodegenerative disease, RNA-binding protein, mediation analysis

DOI

10.1093/bib/bbad007

PMID

36681936

PMCID

PMC10387301

PubMedCentral® Posted Date

1-21-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes