RNA editing and modifications in Creutzfeldt-Jakob disease and other neurodegenerative diseases
2014: 32 months / Grant: 60 000 Euros
Project: The aim of the “RNA editing” project wasto investigate RNA editing in Creutzfeldt-Jakob disease and its potential implication in other neurodegenerative disorders, including Alzheimer’s disease. RNA editing is an epigenetic mechanism that diversifies the cellular trancriptome and proteome, through introduction of chemical modification (deamination) on either Adenosine or Cytidine. Based on recent binary genome:transcriptome comparisons, the researchers proposed the use of murine microglial and prion infected and uninfected neuronal-like cell lines for the identification of RNA editing events in disease-associated transcripts, including Prnp (for CJD) and App (for AD). They further suggested the use of a humanized transgenic mouse model infected with CJD, for establishment of global RNA editing profiles in comparison to healthy animals and RNA editing validation in both mouse and human brain autopsy material. Similarly, based on meta-analysis of pertinent, publically available, RNA-seq data, they proposed establishment of global RNA-editing profilesin Alzheimer’s disease and editing validation in selected transcripts, utilizing human autopsy material. Finally, they proposed RNA editing studies in peripheral blood.
Main results and related published data: Gene expression analyses were performed in the utilized cellular models, as well as on brain tissue from CJD mice and CJD patients, indicating massive deregulation of gene expression profiles in relation to the disease. Further, RNA editing events predicted to be present in the diseased condition were experimentally validated; they are currently being further processed in functional studies, aiming at a better understanding of their contribution to disease progression/pathogenesis. Similarly, Alzheimer’s disease patients’ autopsy material is processed for RNA editing events validation.
The following students/researchers were involved in the project: Athanasios Dimitriadis, Kostantinos Kyritsis, Georgios Sideris-Lampretsas, Eleni Kovaci, Katrin Thune, Eirini Kanata, Dimitra Dafou,Franc Llorens.