Reduced levels of protein recoding by A-to-I RNA editing in Alzheimer's disease
| Autor: | Chaim Wachtel, Erez Y. Levanon, Michal Barak, Eli Eisenberg, Anita Annese, Khen Khermesh, Anna Maria D'Erchia, Ernesto Picardi |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Adenosine Adenosine Deaminase Microfluidics Computational biology Biology Hippocampus Polymerase Chain Reaction Article Epigenesis Genetic 03 medical and health sciences Alzheimer Disease medicine RNA Precursors Coding region Humans Epigenetics Molecular Biology Gene RNA Double-Stranded Genetics Messenger RNA High-Throughput Nucleotide Sequencing RNA-Binding Proteins medicine.disease Inosine Temporal Lobe Frontal Lobe RNA silencing 030104 developmental biology RNA editing ADAR RNA Editing Alzheimer's disease |
| Zdroj: | RNA (New York, N.Y.). 22(2) |
| ISSN: | 1469-9001 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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