Characterization of the myotonic dystrophy region predicts multiple protein isoform-encoding mRNAs.
The mutation underlying myotonic dystrophy (DM) has been identified as an expansion of a polymorphic CTG-repeat in a gene encoding protein kinase activity. Brain and heart transcripts of the DM-kinase (DMR-B15) gene are subject to alternative RNA splicing in both human and mouse. The unstable [CTG]5-30 motif is found uniquely in humans, although the flanking nucleotides are also present in mouse. Characterization of the DM region of both species reveals another active gene (DMR-N9) in close proximity to the kinase gene. DMR-N9 transcripts, mainly expressed in brain and testis, possess a single, large open reading frame, but the function of its protein product is unknown. Clinical manifestation of DM may be caused by the expanded CTG-repeat compromising the (alternative) expression of DM-kinase or DMR-N9 proteins.
Jansen
G
G
Department of Cell Biology and Histology, Faculty of Medical Sciences, University of Nijmegen, The Netherlands.
Mahadevan
M
M
Amemiya
C
C
Wormskamp
N
N
Segers
B
B
Hendriks
W
W
O'Hoy
K
K
Baird
S
S
Sabourin
L
L
Lennon
G
G
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000201:enzymology; D004247:DNA / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009206:Myocardium / Q000201:enzymology; D009223:Myotonic Dystrophy / Q000201:enzymology / Q000235:genetics*; D065636:Myotonin-Protein Kinase; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D016366:Open Reading Frames; D011110:Polymorphism, Genetic; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D013737:Testis / Q000201:enzymology; D014158:Transcription, Genetic
C585517:DMPK protein, human; C585516:DMPK protein, mouse; C081088:DMWD protein, human; C484123:Dm9 protein, mouse; D007527:Isoenzymes; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D011506:Proteins; D012333:RNA, Messenger; D004247:DNA; D011494:Protein Kinases; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases