Abnormalities in A-to-I RNA editing patterns in CNS injuries correlate with dynamic changes in cell type composition

Nurit Gal-Mark, Lea Shallev, Sahar Sweetat, Michal Barak, Jin Billy Li, Erez Y. Levanon, Eli Eisenberg*, Oded Behar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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.

Original languageAmerican English
Article number43421
JournalScientific Reports
Volume7
DOIs
StatePublished - 7 Mar 2017

Bibliographical note

Publisher Copyright:
© 2017 The Author(s).

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