Dr Brendan Ansell - Population Health & Immunity division

Dr Brendan Ansell - Population Health & Immunity division

Location: 
Davis Auditorium
Start Time: 
Wed, 17/06/2020 - 1:00pm
End Time: 
Wed, 17/06/2020 - 2:00pm

Dealing with the editor: RNA editing in human neurons provides genetic clues in neuropsychiatric diseases

Online seminar: access Slido and enter code #WEHIWEDNESDAY
Including Q&A session

​Wednesday seminar hosted by Professor Melanie Bahlo

In the human brain, maturing RNAs are extensively edited by ADAR enzymes. This ‘recoding’ of adenosine to inosine at thousands of sites in the transcriptome originally evolved to distinguish self- from viral RNAs. In humans, RNA editing has acquired a critical role in brain development, and is disrupted in brain diseases. Whereas schizophrenia is associated with excessive editing, autism is associated with hypo-editing, and genetic defects at normally edited sites, produce epilepsy.

To investigate this process in high resolution across the genome, we profiled the ‘editome’ of >3000 neurons from a healthy donor, sequenced on the SMART-seq full-length transcript single cell RNAseq platform. In performing the first RNA editing analysis on this data  we  found that around 25% of the 40,000 edited sites identified in this individual are likely novel RNA editing sites, never before described. We adapted statistical methods for differential methylation analysis to identify  transcripts that are differentially-edited between regions of the cortex, and between excitatory and inhibitory neurons. We also found strong correlations between overall cellular editing rates and expression of small nucleolar RNAs which are known to modulate editing, and are disrupted in autism.

This work provides spatial and cell-type-specific context for published studies of neuropsychiatric conditions, and a detailed reference for forthcoming single-cell studies of the healthy and diseased brain.