Journal Article

Double-stranded RNA-dependent protein kinase, PKR, binds preferentially to Huntington’s disease (HD) transcripts and is activated in HD tissue

Alyson L. Peel, Ram V. Rao, Barbara A. Cottrell, Michael R. Hayden, Lisa M. Ellerby and Dale E. Bredesen

in Human Molecular Genetics

Volume 10, issue 15, pages 1531-1538
Published in print July 2001 | ISSN: 0964-6906
Published online July 2001 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/10.15.1531
Double-stranded RNA-dependent protein kinase, PKR, binds preferentially to Huntington’s disease (HD) transcripts and is activated in HD tissue

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Fourteen neurological diseases have been associated with the expansion of trinucleotide repeat regions. These diseases have been categorized into those that give rise to the translation of toxic polyglutamine proteins and those that are untranslated. Thus far, compelling evidence has not surfaced for the inclusion of a model in which a common mechanism may participate in the pathobiology of both translated and untranslated trinucleotide diseases. In these studies we show that a double-stranded RNA-binding protein, PKR, which has previously been linked to virally-induced and stress-mediated apoptosis, preferentially binds mutant huntingtin RNA transcripts immobilized on streptavidin columns that have been incubated with human brain extracts. These studies also show, by immunodetection in tissue slices, that PKR is present in its activated form in both human Huntington autopsy material and brain tissue derived from Huntington yeast artificial chromosome transgenic mice. The increased immunolocalization of the activated kinase is more pronounced in areas most affected by the disease and, coupled with the RNA binding results, suggests a role for PKR activation in the disease process.

Journal Article.  5224 words.  Illustrated.

Subjects: Genetics and Genomics

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