title: Abnormalities in A-to-I RNA editing patterns in CNS injuries correlate with dynamic changes in cell type composition.
abstract: Adenosine to Inosine (A-to-I) RNA editing is a co- or post-transcriptional mechanism that modifies genomically encoded nucleotides at the RNA level. A-to-I RNA editing is abundant in the brain, and altered editing levels have been reported in various neurological pathologies and following spinal cord injury (SCI). The prevailing concept is that the RNA editing process itself is dysregulated by brain pathologies. Here we analyzed recent RNA-seq data, and found that, except for few mammalian conserved editing sites, editing is significantly higher in neurons than in other cell populations of the brain. We studied A-to-I RNA editing in stab wound injury (SWI) and SCI models and showed that the apparent under-editing observed after injury correlates with an approximately 20% reduction in the relative density of neurons, due to cell death and immune cell infiltration that may account for the observed under-editing. Studies of neuronal and astrocyte cultures and a computational analysis of SCI RNA-seq data further supported the possibility that a reduction in neuronal density is responsible for alterations in the tissue-wide editing patterns upon injury. Thus, our data suggest that the case for a mechanistic linkage between A-to-I RNA editing and brain pathologies should be revisited.
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
authors.forename: Nurit
authors.initials: N
authors.lastname: Gal-Mark
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
authors.forename: Lea
authors.initials: L
authors.lastname: Shallev
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute of Medical Research Israel-Canada (IMRIC), Faculty of Medicine, The Hebrew University, Jerusalem 91120, Israel.
authors.forename: Sahar
authors.initials: S
authors.lastname: Sweetat
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Barak
authors.affiliation: Department of Genetics, Stanford University, Stanford, California 94305, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Billy Li
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
authors.forename: Erez Y
authors.initials: EY
authors.lastname: Levanon
authors.affiliation: Raymond and Beverly Sackler School of Physics and Astronomy and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Eli
authors.initials: E
authors.lastname: Eisenberg
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute of Medical Research Israel-Canada (IMRIC), Faculty of Medicine, The Hebrew University, Jerusalem 91120, Israel.
authors.forename: Oded
authors.initials: O
authors.lastname: Behar
mesh_terms: D000241:Adenosine / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007288:Inosine / Q000235:genetics / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity; D061251:Primary Cell Culture; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D017393:RNA Editing; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D007288:Inosine; D012313:RNA; D000241:Adenosine