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Identification of Tau Stem Loop RNA StabilizersCenter for Neurologic Diseases, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts
Laboratory for Drug Discovery in Neurodegeneration, Brigham & Women's Hospital, Cambridge, Massachusetts
Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts
Laboratory for Drug Discovery in Neurodegeneration, Brigham & Women's Hospital, Cambridge, Massachusetts
Center for Neurologic Diseases, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts, mwolfe{at}rics.bwh.harvard.edu
Alternative splicing of tau exon 10 produces tau isoforms with either 3 (3R) or 4 (4R) repeated microtubule-binding domains. Increased ratios of 4R to 3R tau expression, above the physiological 1:1, leads to neurofibrillary tangles and causes neurodegenerative disease. An RNA stem loop structure plays a significant role in determining the ratio, with decreasing stability correlating with an increase in 4R tau mRNA expression. Recent studies have shown that aminoglycosides are able to bind and stabilize the tau stem loop in vitro, suggesting that other druglike small molecules could be identified and that such molecules might lead to decreased exon 10 splicing in vivo. The authors have developed a fluorescent high-throughput fluorescent binding assay and screened a library of
Key Words: tau • alternative splicing • pyrene • aminoglycosides • RNA
This version was published on September
1, 2007 Journal of Biomolecular Screening, Vol. 12, No. 6,
789-799 (2007) This article has been cited by other articles:
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110,000 compounds to identify candidate drugs that will bind the tau stem loop in vitro. In addition, they have developed a fluorescent-based RNA probe to assay the stabilizing effects of candiate drugs on the tau stem loop RNA. These assays should be applicable to the general problem of identifying small molecules that interact with mRNA secondary structures. (Journal of Biomolecular Screening 2007:789-799) 
