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Biochem Biophys Res Commun. 2000 Oct 22;277(2):518-23.

The CUG-binding protein binds specifically to UG dinucleotide repeats in a yeast three-hybrid system.

Author information

1
Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo, 153-8902, Japan.

Abstract

The CUG-binding protein (CUG-BP) has been reported to be involved in the pathogenesis of myotonic dystrophy (DM) through binding to a CUG trinucleotide repeat located in the 3' untranslated region (3'UTR) of the DM protein kinase (DMPK) gene. We found that CUG-BP associates with long CUG trinucleotide repeats ((CUG)(11)(CUG)(12)), but not with short repeats ((CUG)(12)) in a yeast three-hybrid system. On the other hand, CUG-BP+LYLQ, an alternatively spliced isoform of CUG-BP, does not associate with CUG trinucleotide repeats regardless of the repeat length. In addition to these findings, we found that CUG-BP and CUG-BP+LYLQ strongly and specifically associate with UG dinucleotide repeats. Deletion analyse of CUG-BP revealed that the absence of the first or third RNA-binding domain (RBD I and RBD III, respectively) does not affect the interaction between CUG-BP and UG dinucleotide repeats. Loss of the second RNA-binding domain (RBD II) decreases the affinity of CUG-BP for UG dinucleotide repeats by about 40%. Unexpectedly, deletion of the linker domain most severely reduces the interaction, although this region does not contain a known RNA-binding motif. Our results suggest the possibility that both CUG-BP and CUG-BP+LYLQ associate with UG repeat-containing mRNAs and regulate such metabolic properties as mRNA localization, stability, and translation, and provide new insights into the pathogenesis of DM.

PMID:
11032753
DOI:
10.1006/bbrc.2000.3694
[Indexed for MEDLINE]

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