title: RNA editing generates cellular subsets with diverse sequence within populations.
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.
authors.affiliation: Laboratory of Lymphocyte Biology, The Rockefeller University, New York, New York 10065, USA.
authors.forename: Dewi
authors.initials: D
authors.lastname: Harjanto
authors.affiliation: School of Mathematics and Statistics, University of Glasgow, Glasgow G12 8QW, UK.
authors.forename: Theodore
authors.initials: T
authors.lastname: Papamarkou
authors.affiliation: School of Mathematical and Physical Sciences, University of Technology Sydney, Ultimo, New South Wales 2007, Australia.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Oates
authors.affiliation: Laboratory of Lymphocyte Biology, The Rockefeller University, New York, New York 10065, USA.
authors.forename: Violeta
authors.initials: V
authors.lastname: Rayon-Estrada
authors.affiliation: Laboratory of Lymphocyte Biology, The Rockefeller University, New York, New York 10065, USA.
authors.forename: F Nina
authors.initials: FN
authors.lastname: Papavasiliou
authors.affiliation: Department of Statistics, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Papavasiliou
mesh_terms: D000071479:APOBEC-1 Deaminase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001499:Bayes Theorem; D019070:Cell Lineage; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology* / Q000502:physiology; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D017393:RNA Editing; D015203:Reproducibility of Results; D017423:Sequence Analysis, RNA / Q000706:statistics & numerical data; D059010:Single-Cell Analysis / Q000706:statistics & numerical data
chemical_list: D008070:Lipopolysaccharides; D000071479:APOBEC-1 Deaminase; C000605090:Apobec1 protein, mouse