RT Journal Article
SR Electronic
T1 Cellular and genetic drivers of RNA editing variation in the human brain
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.07.16.452690
DO 10.1101/2021.07.16.452690
A1 Ryn Cuddleston
A1 Junhao Li
A1 Xuanjia Fan
A1 Alexey Kozenkov
A1 Matthew Lalli
A1 Shahrukh Khalique
A1 Stella Dracheva
A1 Eran A. Mukamel
A1 Michael S. Breen
YR 2021
UL http://biorxiv.org/content/early/2021/07/16/2021.07.16.452690.abstract
AB Posttranscriptional adenosine-to-inosine modifications amplify the functionality of RNA molecules in the brain, yet the cellular and genetic regulation of RNA editing is poorly described. We quantified base-specific RNA editing across three major cell populations from the human prefrontal cortex: glutamatergic neurons, medial ganglionic eminence GABAergic neurons, and oligodendrocytes. We found more selective editing and RNA hyper-editing in neurons relative to oligodendrocytes. The pattern of RNA editing was highly cell type-specific, with 189,229 cell type-associated sites. The cellular specificity for thousands of sites was confirmed by single nucleus RNA-sequencing. Importantly, cell type-associated sites were enriched in GTEx RNA-sequencing data, edited ∼twentyfold higher than all other sites, and variation in RNA editing was predominantly explained by neuronal proportions in bulk brain tissue. Finally, we discovered 661,791 cis-editing quantitative trait loci across thirteen brain regions, including hundreds with cell type-associated features. These data reveal an expansive repertoire of highly regulated RNA editing sites across human brain cell types and provide a resolved atlas linking cell types to editing variation and genetic regulatory effects.Competing Interest StatementThe authors have declared no competing interest.