Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy
AV Philips, LT Timchenko, TA Cooper - Science, 1998 - science.org
AV Philips, LT Timchenko, TA Cooper
Science, 1998•science.orgMyotonic dystrophy (DM) is caused by a CTG expansion in the 3′ untranslated region of
the DM gene. One model of DM pathogenesis suggests that RNAs from the expanded allele
create a gain-of-function mutation by the inappropriate binding of proteins to the CUG
repeats. Data presented here indicate that the conserved heterogeneous nuclear
ribonucleoprotein, CUG-binding protein (CUG-BP), may mediate the trans-dominant effect of
the RNA. CUG-BP was found to bind to the human cardiac troponin T (cTNT) pre …
the DM gene. One model of DM pathogenesis suggests that RNAs from the expanded allele
create a gain-of-function mutation by the inappropriate binding of proteins to the CUG
repeats. Data presented here indicate that the conserved heterogeneous nuclear
ribonucleoprotein, CUG-binding protein (CUG-BP), may mediate the trans-dominant effect of
the RNA. CUG-BP was found to bind to the human cardiac troponin T (cTNT) pre …
Myotonic dystrophy (DM) is caused by a CTG expansion in the 3′ untranslated region of the DM gene. One model of DM pathogenesis suggests that RNAs from the expanded allele create a gain-of-function mutation by the inappropriate binding of proteins to the CUG repeats. Data presented here indicate that the conserved heterogeneous nuclear ribonucleoprotein, CUG-binding protein (CUG-BP), may mediate the trans-dominant effect of the RNA. CUG-BP was found to bind to the human cardiac troponin T (cTNT) pre–messenger RNA and regulate its alternative splicing. Splicing of cTNT was disrupted in DM striated muscle and in normal cells expressing transcripts that contain CUG repeats. Altered expression of genes regulated posttranscriptionally by CUG-BP therefore may contribute to DM pathogenesis.
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