title: Possible editing of Alu transcripts in blood cells of sporadic Creutzfeldt-Jakob disease (sCJD).
abstract: Editing of RNA molecules gained major interest when coding mRNA was analyzed. A small, noncoding, Alu DNA element transcript that may act as regulatory RNA in cells was examined in this study. Alu DNA element transcription was determined in buffy coat from healthy humans and human sporadic Creutzfeldt-Jakob disease (sCJD) cases. In addition, non-sCJD controls, mostly dementia cases and Alzheimer's disease (AD) cases, were included. The Alu cDNA sequences were aligned to genomic Alu DNA elements by database search. A comparison of best aligned Alu DNA sequences with our RNA/cDNA clones revealed editing by deamination by ADAR (adenosine deaminase acting on RNA) and APOBEC (apolipoprotein B editing complex). Nucleotide exchanges like a G instead of an A or a T instead of a C in our cDNA sequences versus genomic Alu DNA pointed to recent mutations. To confirm this, our Alu cDNA sequences were aligned not only to genomic human Alu DNA but also to the respective genomic DNA of the chimpanzee and rhesus. Enhanced ADAR correlated with A-G exchanges in dementia, AD, and sCJD was noted when compared to healthy controls as well as APOBEC-related C-T exchanges. The APOBEC-related mutations were higher in healthy controls than in cases suffering from neurodegeneration, with the exception of the dementia group with the prion protein gene (PRNP) MV genotype. Hence, this study may be considered the first real-time analysis of Alu DNA element transcripts with regard to editing of the respective Alu transcripts in human blood cells.
authors.affiliation: German Primate Center, Gottingen, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Kiesel
authors.forename: Toby J
authors.initials: TJ
authors.lastname: Gibson
authors.forename: Barbara
authors.initials: B
authors.lastname: Ciesielczyk
authors.forename: Monika
authors.initials: M
authors.lastname: Bodemer
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Kaup
authors.forename: Walter
authors.initials: W
authors.lastname: Bodemer
authors.forename: Hans
authors.initials: H
authors.lastname: Zischler
authors.forename: Inga
authors.initials: I
authors.lastname: Zerr
mesh_terms: D020087:Alu Elements / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D007562:Creutzfeldt-Jakob Syndrome / Q000209:etiology / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000235:genetics; D011328:Prions / Q000235:genetics; D012313:RNA / Q000235:genetics; D017393:RNA Editing / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D011328:Prions; D012313:RNA