RNA Editing Alterations Define Disease Manifestations in the Progression of Experimental Autoimmune Encephalomyelitis (EAE).
| Title: | RNA Editing Alterations Define Disease Manifestations in the Progression of Experimental Autoimmune Encephalomyelitis (EAE). |
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| Authors: | Dafou D; Department of Genetics, Development, and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece.; Kanata E; Neurodegenerative Diseases Research Group, Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece.; Pettas S; Department of Genetics, Development, and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece.; Bekas N; Department of Genetics, Development, and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece.; Dimitriadis A; Neurodegenerative Diseases Research Group, Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece.; Kempapidou G; Neurodegenerative Diseases Research Group, Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece.; Lagoudaki R; Multiple Sclerosis Center, B' Neurological Department AHEPA Hospital Thessaloniki, Aristotle University of Thessaloniki, 546 36 Thessaloniki, Greece.; Theotokis P; Multiple Sclerosis Center, B' Neurological Department AHEPA Hospital Thessaloniki, Aristotle University of Thessaloniki, 546 36 Thessaloniki, Greece.; Touloumi O; Multiple Sclerosis Center, B' Neurological Department AHEPA Hospital Thessaloniki, Aristotle University of Thessaloniki, 546 36 Thessaloniki, Greece.; Delivanoglou N; Multiple Sclerosis Center, B' Neurological Department AHEPA Hospital Thessaloniki, Aristotle University of Thessaloniki, 546 36 Thessaloniki, Greece.; Kesidou E; Multiple Sclerosis Center, B' Neurological Department AHEPA Hospital Thessaloniki, Aristotle University of Thessaloniki, 546 36 Thessaloniki, Greece.; Xanthopoulos K; Laboratory of Pharmacology, Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece.; Institute of Applied Biosciences, Centre for Research and Technology Hellas, 603 61 Thessaloniki, Greece.; Grigoriadis N; Multiple Sclerosis Center, B' Neurological Department AHEPA Hospital Thessaloniki, Aristotle University of Thessaloniki, 546 36 Thessaloniki, Greece.; Papavasiliou FN; Immune Diversity (D150) Deutsches Krebsforschungszentrum Im Neuenheimer Feld, 280 69120 Heidelberg, Germany.; Sklaviadis T; Neurodegenerative Diseases Research Group, Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece.; Laboratory of Pharmacology, Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece. |
| Source: | Cells [Cells] 2022 Nov 12; Vol. 11 (22). Date of Electronic Publication: 2022 Nov 12. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI |
| MeSH Terms: | RNA Editing*/genetics ; Encephalomyelitis, Autoimmune, Experimental*/genetics; APOBEC-1 Deaminase/genetics ; Humans ; Mice ; Animals ; RNA, Double-Stranded ; Mutagenesis, Site-Directed ; Mice, Knockout |
| Abstract: | 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. |
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| Contributed Indexing: | Keywords: RNA editing; RNA-sequencing; experimental autoimmune encephalomyelitis; gene expression; microglia; multiple sclerosis; neurodegeneration; neuroinflammation |
| Substance Nomenclature: | EC 3.5.4.36 (APOBEC-1 Deaminase); 0 (RNA, Double-Stranded) |
| Entry Date(s): | Date Created: 20221126 Date Completed: 20221129 Latest Revision: 20230115 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC9688714 |
| DOI: | 10.3390/cells11223582 |
| PMID: | 36429012 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't