RNA Editing Alterations Define Disease Manifestations in the Progression of Experimental Autoimmune Encephalomyelitis (EAE)

RNA editing is an epitranscriptomic modification, leading to targeted changes in RNA transcripts. It is mediated by the action of ADAR (adenosine deaminases acting on double-stranded (ds) RNA and APOBEC (apolipoprotein B mRNA editing enzyme catalytic polypeptide-like) deaminases and appears to play...

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Bibliographic Details
Published in:	Cells (Basel, Switzerland) Vol. 11; no. 22; p. 3582
Main Authors:	Dafou, Dimitra, Kanata, Eirini, Pettas, Spyros, Bekas, Nikolaos, Dimitriadis, Athanasios, Kempapidou, Garyfalia, Lagoudaki, Roza, Theotokis, Paschalis, Touloumi, Olga, Delivanoglou, Nikoleta, Kesidou, Evangelia, Xanthopoulos, Konstantinos, Grigoriadis, Nikolaos, Papavasiliou, Fotini Nina, Sklaviadis, Theodoros
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 12-11-2022 MDPI
Subjects:	Alzheimer's disease Animals APOBEC-1 Deaminase - genetics Apolipoprotein B Brain research Central nervous system Development and progression Double-stranded RNA Editing Encephalomyelitis Encephalomyelitis, Autoimmune, Experimental - genetics Enzymes Experimental allergic encephalomyelitis experimental autoimmune encephalomyelitis Gene expression Genetic aspects Genomes Health aspects Humans Immunology Inflammation Inflammatory diseases Mice Mice, Knockout Microglia Multiple sclerosis Mutagenesis, Site-Directed Neurodegeneration Neurodegenerative diseases Pathogenesis Quality control RNA editing RNA Editing - genetics RNA processing RNA, Double-Stranded RNA-sequencing Software Transgenic animals Greece RNA-sequencing RNA editing experimental autoimmune encephalomyelitis neuroinflammation multiple sclerosis neurodegeneration microglia gene expression
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Summary:	RNA editing is an epitranscriptomic modification, leading to targeted changes in RNA transcripts. It is mediated by the action of ADAR (adenosine deaminases acting on double-stranded (ds) RNA and APOBEC (apolipoprotein B mRNA editing enzyme catalytic polypeptide-like) deaminases and appears to play a major role in the pathogenesis of many diseases. Here, we assessed its role in experimental autoimmune encephalomyelitis (EAE), a widely used non-clinical model of autoimmune inflammatory diseases of the central nervous system (CNS), which resembles many aspects of human multiple sclerosis (MS). We have analyzed in silico data from microglia isolated at different timepoints through disease progression to identify the global editing events and validated the selected targets in murine tissue samples. To further evaluate the functional role of RNA editing, we induced EAE in transgenic animals lacking expression of APOBEC-1. We found that RNA-editing events, mediated by the APOBEC and ADAR deaminases, are significantly reduced throughout the course of disease, possibly affecting the protein expression necessary for normal neurological function. Moreover, the severity of the EAE model was significantly higher in APOBEC-1 knock-out mice, compared to wild-type controls. Our results implicate regulatory epitranscriptomic mechanisms in EAE pathogenesis that could be extrapolated to MS and other neurodegenerative disorders (NDs) with common clinical and molecular features.
ISSN:	2073-4409 2073-4409
DOI:	10.3390/cells11223582