Nucleic Acids Research, Vol 24, Issue 22 4407-4414, Copyright © 1996 by Oxford University Press
LT Timchenko, JW Miller, NA Timchenko, DR DeVore, KV Datar, L Lin, R Roberts, CT Caskey and MS Swanson
Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease that
is associated with a (CTG)n repeat expansion in the 3'- untranslated region
of the myotonin protein kinase (Mt-PK) gene. This study reports the
isolation and characterization of a (CUG)n triplet repeat pre-mRNA/mRNA
binding protein that may play an important role in DM pathogenesis. Two
HeLa cell proteins, CUG-BP1 and CUG-BP2, have been purified based upon
their ability to bind specifically to (CUG)8 oligonucleotides in vitro.
While CUG-BP1 is the major (CUG)8-binding activity in normal cells, nuclear
CUG-BP2 binding activity increases in DM cells. Both CUG-BP1 and CUG-BP2
have been identified as isoforms of a novel heterogeneous nuclear
ribonucleoprotein (hnRNP), hNab50. The CUG-BP/hNab50 protein is localized
predominantly in the nucleus and is associated with polyadenylated RNAs in
vivo. In vitro RNA- binding/photocrosslinking studies demonstrate that
CUG-BP/hNab50 binds to RNAs containing the Mt-PK 3'-UTR. We propose that
the (CUG)n repeat region in Mt-PK mRNA is a binding site for CUG-BP/hNab50
in vivo, and triplet repeat expansion leads to sequestration of this hnRNP
on mutant Mt-PK transcripts.
ARTICLES
Identification of a (CUG)n triplet repeat RNA-binding protein and its expression in myotonic dystrophy
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
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