Overexpression of CUGBP1 in skeletal muscle from adult classic myotonic dystrophy type 1 but not from myotonic dystrophy type 2

Rosanna Cardani, Enrico Bugiardini, Laura V. Renna, Giulia Rossi, Graziano Colombo, Rea Valaperta, Giuseppe Novelli, Annalisa Botta, Giovanni Meola

Research output: Contribution to journalArticle

Abstract

Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are progressive multisystemic disorders caused by similar mutations at two different genetic loci. The common key feature of DM pathogenesis is nuclear accumulation of mutant RNA which causes aberrant alternative splicing of specific pre-mRNAs by altering the functions of two RNA binding proteins, MBNL1 and CUGBP1. However, DM1 and DM2 show disease-specific features that make them clearly separate diseases suggesting that other cellular and molecular pathways may be involved. In this study we have analysed the histopathological, and biomolecular features of skeletal muscle biopsies from DM1 and DM2 patients in relation to presenting phenotypes to better define the molecular pathogenesis. Particularly, the expression of CUGBP1 protein has been examined to clarify if this factor may act as modifier of disease-specific manifestations in DM. The results indicate that the splicing and muscle pathological alterations observed are related to the clinical phenotype both in DM1 and in DM2 and that CUGBP1 seems to play a role in classic DM1 but not in DM2. In conclusion, our results indicate that multisystemic disease spectrum of DM pathologies may not be explained only by spliceopathy thus confirming that the molecular pathomechanism of DM is more complex than that actually suggested.

Original languageEnglish
Article numbere83777
JournalPLoS One
Volume8
Issue number12
DOIs
Publication statusPublished - Dec 20 2013

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Myotonic Dystrophy
Muscle
skeletal muscle
Skeletal Muscle
pathogenesis
phenotype
RNA-binding proteins
modifiers (genes)
alternative splicing
biopsy
protein synthesis
RNA
Phenotype
mutation
muscles
mutants
loci
Genetic Loci
RNA-Binding Proteins
Biopsy

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Overexpression of CUGBP1 in skeletal muscle from adult classic myotonic dystrophy type 1 but not from myotonic dystrophy type 2. / Cardani, Rosanna; Bugiardini, Enrico; Renna, Laura V.; Rossi, Giulia; Colombo, Graziano; Valaperta, Rea; Novelli, Giuseppe; Botta, Annalisa; Meola, Giovanni.

In: PLoS One, Vol. 8, No. 12, e83777, 20.12.2013.

Research output: Contribution to journalArticle

Cardani, Rosanna ; Bugiardini, Enrico ; Renna, Laura V. ; Rossi, Giulia ; Colombo, Graziano ; Valaperta, Rea ; Novelli, Giuseppe ; Botta, Annalisa ; Meola, Giovanni. / Overexpression of CUGBP1 in skeletal muscle from adult classic myotonic dystrophy type 1 but not from myotonic dystrophy type 2. In: PLoS One. 2013 ; Vol. 8, No. 12.
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