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nature structural & molecular biology VOLUME 17 NUMBER 2 FEBRUARY 2010 187 a rt i c l e s

Summary: nature structural & molecular biology VOLUME 17 NUMBER 2 FEBRUARY 2010 187
a rt i c l e s
Myotonic dystrophy (DM) is a triplet-repeat expansion disease, one of
a group that includes Huntington's disease, Fragile X syndrome and
Friedreich's ataxia1,2. The common form, DM1, is caused by a CTG-
repeat expansion (CTGexp) in the 3 untranslated region (UTR) of the
myotonic dystrophy protein kinase (DMPK) gene,leading to myotonia,
muscle degeneration, reduced heart function, ocular cataracts and
nervous system dysfunction3. RNA containing CUG repeats (CUGexp
RNA) accumulates in nuclear foci4,5. Based on its autosomal dominant
inheritance, a leading hypothesis for the cause of DM1 is that CUGexp
RNA is toxic. Mice engineered to express CUGexp RNA show many
symptoms of myotonic dystrophy6,7.In addition to altering RNA splicing
(see below), CUGexp RNA has been proposed to disrupt a wide variety
of cellular processes through several mechanisms, including"leaching"
of transcription factors8, being processed into small RNAs that trigger
inappropriate gene silencing9 or activating PKC-dependent signaling
pathways10. Among these, the contribution of splicing perturbations is
most clear given the physiological relevance of several splicing alterations
that occur when CUGexp RNA is expressed5,7,11. For example, aberrant


Source: Ares Jr., Manny - Department of Molecular, Cell, and Developmental Biology, University of California at Santa Cruz


Collections: Biology and Medicine