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Muscleblind protein, MBNL1/EXP, binds specifically to CHHG repeats

Kino, Yoshihiro ; Mori, Daisuke ; Oma, Yoko ; Takeshita, Yuya ; Sasagawa, Noboru ; Ishiura, Shoichi

Human molecular genetics, 2004-03, Vol.13 (5), p.495-507 [Periódico revisado por pares]

Oxford: Oxford University Press

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Título:
Muscleblind protein, MBNL1/EXP, binds specifically to CHHG repeats
Autor: Kino, Yoshihiro ; Mori, Daisuke ; Oma, Yoko ; Takeshita, Yuya ; Sasagawa, Noboru ; Ishiura, Shoichi
Assuntos: Alternative Splicing - genetics ; Biological and medical sciences ; CELF Proteins ; Classical genetics, quantitative genetics, hybrids ; CUG-BP protein ; DNA Primers ; eIF-2 Kinase - metabolism ; Electrophoretic Mobility Shift Assay ; EXP protein ; Fundamental and applied biological sciences. Psychology ; Gene Components ; Genetics of eukaryotes. Biological and molecular evolution ; Glutathione Transferase - metabolism ; Human ; Humans ; MBNL1 protein ; Molecular and cellular biology ; Myotonic dystrophy ; Myotonic Dystrophy - genetics ; Myotonic Dystrophy - metabolism ; PKR protein ; Repetitive Sequences, Nucleic Acid - genetics ; Repetitive Sequences, Nucleic Acid - physiology ; RNA-Binding Proteins - genetics ; RNA-Binding Proteins - metabolism ; Transformation, Bacterial ; Two-Hybrid System Techniques ; ZNF9 gene
É parte de: Human molecular genetics, 2004-03, Vol.13 (5), p.495-507
Notas: To whom correspondence should be addressed. Tel/Fax: +81 354546739; Email: cishiura@mail.ecc.u-tokyo.ac.jp
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Descrição: Myotonic dystrophy (DM) type 1 is caused by an expansion of a CTG repeat in the DMPK gene and type 2 by a CCTG repeat in the ZNF9 gene. Previous reports have suggested that transcripts containing expanded CUG/CCUG repeats might have toxic gain-of-function effects, probably affecting the function of RNA-binding proteins in the pathogenesis of DM. Here, it was attempted to compare the RNA-binding properties of three proteins, CUG-BP, MBNL1/EXP and PKR, which have previously been suggested to interact with CUG repeats. MBNL1, but not CUG-BP or PKR, interacted with both CUG and CCUG repeats in a yeast three-hybrid system. By using various synthetic RNAs, it was found that MBNL1 specifically interacts with repetitive sequences summarized as CHHG and CHG repeats, where H is A, U or C. Interestingly, MBNL1 did not interact with a genuine double-stranded RNA comprising CAG/CUG repeats, suggesting that MBNL1 prefers bulge-containing double-stranded RNAs. Deletion analysis indicates a difference in RNA-binding abilities among splice variants of MBNL1. It was also found that MBNL1 can bind to repetitive motifs in ZNF9, which contain a minimal length of CCUG repeats with non-CCUG insertions.
Editor: Oxford: Oxford University Press
Idioma: Inglês

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Muscleblind protein, MBNL1/EXP, binds specifically to CHHG repeats

Kino, Yoshihiro ; Mori, Daisuke ; Oma, Yoko ; Takeshita, Yuya ; Sasagawa, Noboru ; Ishiura, Shoichi

Oxford: Oxford University Press

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