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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
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 | ||||||||
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| 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: |
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| 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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