Muscleblind-like protein 1 nuclear sequestration is a molecular pathology marker of DM1 and DM2.
Myotonic dystrophies (DM) are repeat expansion diseases in which expanded CTG (DM1) and CCTG (DM2) repeats cause the disease. Mutant transcripts containing CUG/CCUG repeats are retained in muscle nuclei producing ribonuclear inclusions, which can bind specific RNA-binding proteins, leading to a reduction in their activity. The sequestration of muscleblind-like proteins (MBNLs), a family of alternative splicing factors, appears to be involved in splicing defects characteristic of DM pathologies. To determine whether MBNL1 nuclear sequestration is a feature of DM pathologies, we have examined the in vivo distribution of MBNL1 in muscle sections from genetically confirmed DM1 (n=7) and DM2 (n=9) patients, patients with other myotonic disorders (n=11) and from patients with disorders caused by repeat expansions, but not DM1/DM2 (n=3). The results of our immunofluorescence study indicate that, among patients examined, MBNL1 nuclear sequestration in protein foci is a molecular pathology marker of DM1 and DM2 patients where ribonuclear inclusions of transcripts with expanded CUG/CCUG repeats are also present. These findings indicate that MBNLs might be important targets for therapeutic interventions to correct some of the specific features of DM pathology.
Cardani
R
R
Department of Molecular Biology and Biotechnologies, University of Milan, Italy.
Mancinelli
E
E
Rotondo
G
G
Sansone
V
V
Meola
G
G
D002467:Cell Nucleus; D042622:DNA Repeat Expansion; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D009223:Myotonic Dystrophy / Q000145:classification / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D005819:Genetic Markers; C493663:MBNL1 protein, human; D016601:RNA-Binding Proteins