title: Reduced levels of protein recoding by A-to-I RNA editing in Alzheimer's disease.
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.
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 59002, Israel.
authors.forename: Khen
authors.initials: K
authors.lastname: Khermesh
authors.affiliation: Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, Bari, 70126, Italy Institute of Biomembranes and Bioenergetics, National Research Council, Bari, 70126, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: D'Erchia
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 59002, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Barak
authors.affiliation: Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, Bari, 70126, Italy.
authors.forename: Anita
authors.initials: A
authors.lastname: Annese
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 59002, Israel.
authors.forename: Chaim
authors.initials: C
authors.lastname: Wachtel
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 59002, Israel.
authors.forename: Erez Y
authors.initials: EY
authors.lastname: Levanon
authors.affiliation: Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, Bari, 70126, Italy Institute of Biomembranes and Bioenergetics, National Research Council, Bari, 70126, Italy.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Picardi
authors.affiliation: Sagol School of Neuroscience and Raymond and Beverly Sackler School of Physics and Astronomy, Tel Aviv University, Tel Aviv, 69978, Israel.
authors.forename: Eli
authors.initials: E
authors.lastname: Eisenberg
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000243:Adenosine Deaminase / Q000235:genetics* / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D044127:Epigenesis, Genetic; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007288:Inosine / Q000378:metabolism; D044085:Microfluidics; D016133:Polymerase Chain Reaction; D017393:RNA Editing; D012322:RNA Precursors / Q000235:genetics* / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology
chemical_list: D012322:RNA Precursors; D012330:RNA, Double-Stranded; D016601:RNA-Binding Proteins; D007288:Inosine; C000595356:ADAR protein, human; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase; D000241:Adenosine
keywords: Alzheimer disease; RNA editing; epigenetics; targeted resequencing