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- Title
RNA leaching of transcription factors disrupts transcription in myotonic dystrophy.
- Authors
Ebralidze, A; Wang, Y; Petkova, V; Ebralidse, K; Junghans, R P
- Abstract
Myotonic dystrophy type 1 (DM1) is caused by a CUGn expansion (n approximately 50 to 5000) in the 3' untranslated region of the mRNA of the DM protein kinase gene. We show that mutant RNA binds and sequesters transcription factors (TFs), with up to 90% depletion of selected TFs from active chromatin. Diverse genes are consequently reduced in expression, including the ion transporter CIC-1, which has been implicated in myotonia. When TF specificity protein 1 (Sp1) was overexpressed in DM1-affected cells, low levels of messenger RNA for CIC-1 were restored to normal. Transcription factor leaching from chromatin by mutant RNA provides a potentially unifying pathomechanistic explanation for this disease.
- Publication
Science (New York, N.Y.), 2004, Vol 303, Issue 5656, p383
- ISSN
1095-9203
- Publication type
Journal Article
- DOI
10.1126/science.1088679