RNA editing generates cellular subsets with diverse sequence within populations

Harjanto, D., Papamarkou, T. , Oates, C. J., Rayon-Estrada, V., Papavasiliou, F. N. and Papavasiliou, A. (2016) RNA editing generates cellular subsets with diverse sequence within populations. Nature Communications, 7, 12145. (doi: 10.1038/ncomms12145) (PMID:27418407) (PMCID:PMC4947178)

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: Articles
• Additional Information: D.H. was supported by NIH F32CA183318. T.P. and A.P. were supported by Leverhulme project grant RPG-2013-270. V.R.E. and F.N.P. were supported by Starr Cancer Consortium grant I7-A767. C.J.O. was supported by UK EPSRC grant ‘Centre for Research in Statistical Methodology’ EP/D002060/1.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Papamarkou, Dr Theodore
• Authors: Harjanto, D., Papamarkou, T., Oates, C. J., Rayon-Estrada, V., Papavasiliou, F. N., and Papavasiliou, A.
• College/School: College of Science and Engineering > School of Mathematics and Statistics > Statistics
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2016 The Authors
• First Published: First published in Nature Communications 7: 12145
• Publisher Policy: Reproduced under a Creative Commons License