Reduced levels of protein recoding by A-to-I RNA editing in Alzheimer's disease |
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Authors: | Khen Khermesh Anna Maria D'Erchia Michal Barak Anita Annese Chaim Wachtel Erez Y Levanon Ernesto Picardi Eli Eisenberg |
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Institution: | 1.Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 59002, Israel;2.Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, Bari, 70126, Italy;3.Institute of Biomembranes and Bioenergetics, National Research Council, Bari, 70126, Italy;4.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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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. |
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Keywords: | Alzheimer disease epigenetics RNA editing targeted resequencing |
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