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Lubov Timchenko - One of the best experts on this subject based on the ideXlab platform.
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cardiac elav type rna binding protein etr 3 binds to rna cug repeats expanded in myotonic dystrophy
Human Molecular Genetics, 1999Co-Authors: Xiaohui Lu, Nikolaj A Timchenko, Lubov TimchenkoAbstract:: 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)8repeats. 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.
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identification of a cug n triplet repeat rna binding protein and its expression in myotonic dystrophy
Nucleic Acids Research, 1996Co-Authors: Lubov Timchenko, Jill W Miller, Nikolaj A Timchenko, Druery R Devore, Kshama V Datar, Lijun Lin, Robert Roberts, Thomas C Caskey, Maurice S SwansonAbstract: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.
Maurice S Swanson - One of the best experts on this subject based on the ideXlab platform.
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identification of a cug n triplet repeat rna binding protein and its expression in myotonic dystrophy
Nucleic Acids Research, 1996Co-Authors: Lubov Timchenko, Jill W Miller, Nikolaj A Timchenko, Druery R Devore, Kshama V Datar, Lijun Lin, Robert Roberts, Thomas C Caskey, Maurice S SwansonAbstract: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.
Nikolaj A Timchenko - One of the best experts on this subject based on the ideXlab platform.
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cardiac elav type rna binding protein etr 3 binds to rna cug repeats expanded in myotonic dystrophy
Human Molecular Genetics, 1999Co-Authors: Xiaohui Lu, Nikolaj A Timchenko, Lubov TimchenkoAbstract:: 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)8repeats. 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.
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identification of a cug n triplet repeat rna binding protein and its expression in myotonic dystrophy
Nucleic Acids Research, 1996Co-Authors: Lubov Timchenko, Jill W Miller, Nikolaj A Timchenko, Druery R Devore, Kshama V Datar, Lijun Lin, Robert Roberts, Thomas C Caskey, Maurice S SwansonAbstract: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.
Gloria Vergara - One of the best experts on this subject based on the ideXlab platform.
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tissue and tumor mosaicism of the myotonin protein Kinase gene trinucleotide repeat in a patient with multiple basal cell carcinomas associated with myotonic dystrophy
Journal of The American Academy of Dermatology, 2004Co-Authors: Jose Banuls, Rafael Botella, Francesc Palau, Regina Ramon, Carmina Diaz, Artemio Paya, Lucia Carnero, Gloria VergaraAbstract:We describe the third case (to our knowledge) of multiple basal cell carcinoma associated with myotonic dystrophy and carry out a genetic study of the tumor comparing it with healthy skin. We consider that our results show that this association might be not a purely random phenomenon and that the particular genetic characteristics of this disorder might have a role in the pathogenesis of the tumor.
Koichi Suzuki - One of the best experts on this subject based on the ideXlab platform.
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expression of a novel human myotonin protein Kinase mtpk cdna clone which encodes a protein with a thymopoietin like domain in cos cells
FEBS Letters, 1994Co-Authors: Noboru Sasagawa, Hiroyuki Sorimachi, Kei Maruyama, Kiichi Arahata, Shoichi Ishiura, Koichi SuzukiAbstract:A full-length cDNA of human myotonin protein Kinase (MtPK) was cloned and expressed in COS-1 cells. MtPK is recovered from the cytosolic fraction of the COS extract as a 70 kDa protein, which coincides with the size deduced from the predicted amino acid sequence. The sequence has a significant homology to thymopoietin, a peptide hormone of the thymus. Biochemical characteristics of MtPK expressed in COS-1 cells and its expression in rat tissues are investigated.
