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EMBO Rep. 2011 Jul 1;12(7):735-42. doi: 10.1038/embor.2011.86.

RNA steady-state defects in myotonic dystrophy are linked to nuclear exclusion of SHARP.

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Department of Biochemistry and Molecular Biology, Institute for Genetic Medicine, 2250 Alcazar Street, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.


We describe a new mechanism by which CTG tract expansion affects myotonic dystrophy (DM1). Changes to the levels of a panel of RNAs involved in muscle development and function that are downregulated in DM1 are due to aberrant localization of the transcription factor SHARP (SMART/HDAC1-associated repressor protein). Mislocalization of SHARP in DM1 is consistent with increased CRM1-mediated export of SHARP to the cytoplasm. A direct link between CTG repeat expression and SHARP mislocalization is demonstrated as expression of expanded CTG repeats in normal cells recapitulates cytoplasmic SHARP localization. These results demonstrate a role for the inactivation of SHARP transcription in DM1 biology.

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