Nov 14, 2019

Cell type and cortex-specific RNA editing in single human neurons informs neuropsychiatric disorders

BioRxiv : the Preprint Server for Biology
Brendan Robert E. AnsellMelanie Bahlo

Abstract

Conversion of adenosine to inosine in RNA by ADAR enzymes occurs at thousands of sites in the human transcriptome, and is essential for healthy brain development. This process, known as 'RNA editing', is dysregulated in many neuropsychiatric diseases, but is little understood at the level of individual neurons. We examined full-length nuclear transcriptomes of 3,055 neurons from six cortical regions of a neurotypical post-mortem female donor and identified 40,861 high-confidence edited sites. The majority of sites were located within Alu repeats in introns or 3' UTRs, and were present in previously published RNA editing databases. We identified 15,784 putative novel RNA editing sites, 30% of which were also detectable in independently generated neuronal transcriptomes from unrelated donors. The strongest correlates of global editing rates were expression levels of small nucleolar RNAs from the SNORD115 and SNORD116 cluster (15q11), known to modulate serotonin receptor processing and to colocalize with ADAR2, one of three known RNA editing enzymes in humans. As expected, expression of DNA and RNA binding proteins were negatively associated with editing. We present evidence for dysregulated RNA editing in six rare genetic conditi...Continue Reading

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Mentioned in this Paper

Study
Adenosine
Neurons
Inosine
Brain
Donor Person
Small Nucleolar RNA Location
RNA Editing
Site
Alu Elements

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