RNA editing generates cellular subsets with diverse sequence within populations

Dewi Harjanto, Theodore Papamarkou, Chris J. Oates, Violeta Rayon-Estrada, F. Nina Papavasiliou () and Anastasia Papavasiliou ()
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Dewi Harjanto: Laboratory of Lymphocyte Biology, The Rockefeller University
Theodore Papamarkou: School of Mathematics and Statistics, University of Glasgow
Chris J. Oates: School of Mathematical and Physical Sciences, University of Technology Sydney
Violeta Rayon-Estrada: Laboratory of Lymphocyte Biology, The Rockefeller University
F. Nina Papavasiliou: Laboratory of Lymphocyte Biology, The Rockefeller University
Anastasia Papavasiliou: University of Warwick

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract RNA editing is a mutational mechanism that specifically alters the nucleotide content in transcribed RNA. However, editing rates vary widely, and could result from equivalent editing amongst individual cells, or represent an average of variable editing within a population. Here we present a hierarchical Bayesian model that quantifies the variance of editing rates at specific sites using RNA-seq data from both single cells, and a cognate bulk sample to distinguish between these two possibilities. The model predicts high variance for specific edited sites in murine macrophages and dendritic cells, findings that we validated experimentally by using targeted amplification of specific editable transcripts from single cells. The model also predicts changes in variance in editing rates for specific sites in dendritic cells during the course of LPS stimulation. Our data demonstrate substantial variance in editing signatures amongst single cells, supporting the notion that RNA editing generates diversity within cellular populations.

Date: 2016
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DOI: 10.1038/ncomms12145

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