The identification and characterization of oxidized RNAs in Alzheimer's disease.
It has been shown that cytoplasmic RNA oxidation occurs to a great extent in the brains of Alzheimer's disease (AD) patients. The goal of this study was to isolate and identify oxidized RNA species in AD. We show that significant amounts of poly(A)+ mRNAs are oxidized in AD brains. RNA oxidation is not random but highly selective. Importantly, many identified oxidized mRNA species have been implicated in the pathogenesis of AD. Quantitative analysis revealed that some mRNA species are more susceptible to oxidative damage. We also investigated the biological consequence of oxidatively damaged mRNAs by expressing them in cell lines. Our data indicated that abnormal processing of proteins occurred to the oxidized mRNAs. This may implicate the potential contribution of RNA oxidation in the pathogenesis of AD.
Shan
Xiu
X
Department of Neuroscience, The Ohio State University, Columbus, Ohio 43210, USA.
Tashiro
Hirofumi
H
Lin
Chien-liang Glenn
CL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002999:Clone Cells; D005625:Frontal Lobe / Q000737:chemistry / Q000378:metabolism; D049452:Green Fluorescent Proteins; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016877:Oxidants / Q000737:chemistry / Q000494:pharmacology; D010084:Oxidation-Reduction; D016716:PC12 Cells; D011061:Poly A / Q000737:chemistry / Q000378:metabolism; D011233:Precipitin Tests; D014176:Protein Biosynthesis; D021381:Protein Transport / Q000187:drug effects; D012313:RNA / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D008164:Luminescent Proteins; D016877:Oxidants; D049452:Green Fluorescent Proteins; D011061:Poly A; D012313:RNA; D008156:Luciferases