Journal Article

Cardiac Elav-type RNA-binding Protein (ETR-3) Binds to RNA CUG Repeats Expanded in Myotonic Dystrophy

Xiaohui Lu, Nikolai A. Timchenko and Lubov T. Timchenko

in Human Molecular Genetics

Volume 8, issue 1, pages 53-60
Published in print January 1999 | ISSN: 0964-6906
Published online January 1999 | e-ISSN: 1460-2083 | DOI:
Cardiac Elav-type RNA-binding Protein (ETR-3) Binds to RNA CUG Repeats Expanded in Myotonic Dystrophy

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Myotonic dystrophy (DM) is a neuromuscular disorder associated with CTG triplet repeat expansion in the myotonin protein kinase gene (DMPK). We previously proposed a hypothesis suggesting that the expanded CUG repeats sequester specific RNA-binding proteins and that such a sequestration results in abnormal RNA processing of several RNAs containing CUG repeats in multiple tissues affected in patients with DM. One of the members of the CUG-binding proteins, CUG-BP, has been identified previously. Here we describe the second member of this family, elav-type ribonucleoprotein (ETR-3), which is highly expressed in heart and is able to interact with CUG repeats. Screening of a mouse liver cDNA library with a CUG-BP probe identified two mETR-3 cDNAs. Two additional cDNAs from mouse heart were amplified by RT-PCR. These cDNAs differ by several insertions/deletions and might be generated via alternative splicing. Mouse ETR-3 has a mol. wt of 50 kDa and displays a high level of homology to CUG-BP protein. The organization of the RNA-binding domains (RBDs) within the ETR-3 molecule is similar to one within CUG-BP. A study of mETR-3 RNA-binding activity showed that the mETR-3 binds to (CUG)8 repeats. Sequence analysis of mETR-3 indicates the presence of several CUG repeats within the mETR-3 mRNA. Both CUG-BP and mETR-3 bind to mETR-3 mRNA via CUG repeats, suggesting the possible involvement of CUG-BP-like proteins in the regulation of mETR-3 processing. Analysis of the tissue distribution of ETR-3 showed that in human cells, ETR-3 mRNA is highly expressed in heart, but is undetectable in other tissues examined. Our results suggest the existence of a family of proteins that bind to CUG repeats and might be affected in DM by expansion of CUG repeats.

Journal Article.  6351 words.  Illustrated.

Subjects: Genetics and Genomics

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