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PMID: 26655226 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Reduced levels of protein recoding by A-to-I RNA editing in Alzheimer's disease.

RNA (New York, N.Y.) ·Vol. 22 ·No. 2 ·2016-02-00 ·Pages 290-302

Khermesh K, D'Erchia AM, Barak M, Annese A, Wachtel C, Levanon EY, Picardi E, Eisenberg E

Abstract

Adenosine to inosine (A-to-I) RNA editing, catalyzed by the ADAR enzyme family, acts on dsRNA structures within pre-mRNA molecules. Editing of the coding part of the mRNA may lead to recoding, amino acid substitution in the resulting protein, possibly modifying its biochemical and biophysical properties. Altered RNA editing patterns have been observed in various neurological pathologies. Here, we present a comprehensive study of recoding by RNA editing in Alzheimer's disease (AD), the most common cause of irreversible dementia. We have used a targeted resequencing approach supplemented by a microfluidic-based high-throughput PCR coupled with next-generation sequencing to accurately quantify A-to-I RNA editing levels in a preselected set of target sites, mostly located within the coding sequence of synaptic genes. Overall, editing levels decreased in AD patients' brain tissues, mainly in the hippocampus and to a lesser degree in the temporal and frontal lobes. Differential RNA editing levels were observed in 35 target sites within 22 genes. These results may shed light on a possible association between the neurodegenerative processes typical for AD and deficient RNA editing.

Keywords
Alzheimer disease RNA editing epigenetics targeted resequencing
MeSH Terms
Adenosine/metabolism Adenosine Deaminase/genetics,metabolism Alzheimer Disease/genetics,metabolism,pathology Epigenesis, Genetic Frontal Lobe/metabolism,pathology High-Throughput Nucleotide Sequencing Hippocampus/metabolism,pathology Humans Inosine/metabolism Microfluidics Polymerase Chain Reaction RNA Editing RNA Precursors/genetics,metabolism RNA, Double-Stranded/genetics,metabolism RNA-Binding Proteins/genetics,metabolism Temporal Lobe/metabolism,pathology
Chemicals
RNA Precursors RNA, Double-Stranded RNA-Binding Proteins Inosine ADAR protein, human ADARB1 protein, human Adenosine Deaminase Adenosine
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Khermesh Khen
Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 59002, Israel.
D'Erchia Anna Maria
Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, Bari, 70126, Italy Institute of Biomembranes and Bioenergetics, National Research Council, Bari, 70126, Italy.
Barak Michal
Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 59002, Israel.
Annese Anita
Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, Bari, 70126, Italy.
Wachtel Chaim
Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 59002, Israel.
Levanon Erez Y
Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 59002, Israel.
Picardi Ernesto
Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, Bari, 70126, Italy Institute of Biomembranes and Bioenergetics, National Research Council, Bari, 70126, Italy.
Eisenberg Eli
Sagol School of Neuroscience and Raymond and Beverly Sackler School of Physics and Astronomy, Tel Aviv University, Tel Aviv, 69978, Israel.
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Article Info
Journal
RNA (New York, N.Y.)
Abbr.
RNA
ISSN
1469-9001
DOI
10.1261/rna.054627.115
Published
2016-02-00
Epub
2015-00-11
Pages
290-302
Language
English
Region
United States
NLM ID
9509184
PMCID
PMC4712678
Subset
IM
Grants
European Research Council · 311257 · International
External Links
PubMed source DOI: 10.1261/rna.054627.115 PMC Full Text View journal details
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