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Sci Rep. 2017 Mar 7;7:43421. doi: 10.1038/srep43421.

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

Author information

1
Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
2
Department of Developmental Biology and Cancer Research, Institute of Medical Research Israel-Canada (IMRIC), Faculty of Medicine, The Hebrew University, Jerusalem 91120, Israel.
3
Department of Genetics, Stanford University, Stanford, California 94305, USA.
4
Raymond and Beverly Sackler School of Physics and Astronomy and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.

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.

PMID:
28266523
PMCID:
PMC5339895
DOI:
10.1038/srep43421
[Indexed for MEDLINE]
Free PMC Article

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