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RNA editing generates cellular subsets with diverse sequence within populations

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Harjanto, D., Papamarkou, Theodore, Oates, Chris J., Rayon-Estrada, V., Papavasiliou, F. N. and Papavasiliou, Anastasia (2016) RNA editing generates cellular subsets with diverse sequence within populations. Nature Communications, 7 . 12145 . doi:10.1038/ncomms12145 ISSN 2041-1723.

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Official URL: http://dx.doi.org/10.1038/ncomms12145

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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.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
Divisions: Faculty of Science, Engineering and Medicine > Science > Statistics
Library of Congress Subject Headings (LCSH): RNA, Nucleotides, Cells
Journal or Publication Title: Nature Communications
Publisher: Nature Publishing Group
ISSN: 2041-1723
Official Date: 15 July 2016
Dates:
DateEvent
15 July 2016Published
6 June 2016Accepted
2 January 2016Submitted
Volume: 7
Article Number: 12145
DOI: 10.1038/ncomms12145
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 13 July 2016
Funder: National Institute for Health Research (Great Britain) (NIHR), Leverhulme Trust (LT), Starr Foundation, Engineering and Physical Sciences Research Council (EPSRC), University of Warwick
Grant number: F32CA183318 (NIH), RPG-2013-270 (Leverhulme Trust), I7-A767 (Starr Foundation), EP/D002060/1 (EPSRC)

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