title: Reovirus-mediated induction of ADAR1 (p150) minimally alters RNA editing patterns in discrete brain regions.
abstract: Transcripts encoding ADAR1, a double-stranded, RNA-specific adenosine deaminase involved in the adenosine-to-inosine (A-to-I) editing of mammalian RNAs, can be alternatively spliced to produce an interferon-inducible protein isoform (p150) that is up-regulated in both cell culture and in vivo model systems in response to pathogen or interferon stimulation. In contrast to other tissues, p150 is expressed at extremely low levels in the brain and it is unclear what role, if any, this isoform may play in the innate immune response of the central nervous system (CNS) or whether the extent of editing for RNA substrates critical for CNS function is affected by its induction. To investigate the expression of ADAR1 isoforms in response to viral infection and subsequent alterations in A-to-I editing profiles for endogenous ADAR targets, we used a neurotropic strain of reovirus to infect neonatal mice and quantify A-to-I editing in discrete brain regions using a multiplexed, high-throughput sequencing strategy. While intracranial injection of reovirus resulted in a widespread increase in the expression of ADAR1 (p150) in multiple brain regions and peripheral organs, significant changes in site-specific A-to-I conversion were quite limited, suggesting that steady-state levels of p150 expression are not a primary determinant for modulating the extent of editing for numerous ADAR targets in vivo.
authors.affiliation: Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hood
authors.affiliation: Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Morabito
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Martinez
authors.affiliation: Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: James A
authors.initials: JA
authors.lastname: Gilbert
authors.affiliation: Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Ferrick
authors.affiliation: Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, United States.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Ayers
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: James D
authors.initials: JD
authors.lastname: Chappell
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, United States; Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, United States.
authors.forename: Terence S
authors.initials: TS
authors.lastname: Dermody
authors.affiliation: Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville, TN, United States; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, United States; Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN, United States. Electronic address: ron.emeson@vanderbilt.edu.
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Emeson
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism*; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D001921:Brain / Q000033:anatomy & histology* / Q000254:growth & development / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D017393:RNA Editing / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012087:Reoviridae / Q000235:genetics / Q000502:physiology*
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C000595151:ADAR2 protein, mouse; D000243:Adenosine Deaminase
keywords: Cerebellum; Frontal cortex; High-throughput sequencing; Hippocampus; Interferon