Histochemistry and Cell Biology

, Volume 135, Issue 4, pp 419–425

RNA processing is altered in skeletal muscle nuclei of patients affected by myotonic dystrophy

  • Manuela Malatesta
  • Marzia Giagnacovo
  • Rosanna Cardani
  • Giovanni Meola
  • Carlo Pellicciari
Short communication

DOI: 10.1007/s00418-011-0797-z

Cite this article as:
Malatesta, M., Giagnacovo, M., Cardani, R. et al. Histochem Cell Biol (2011) 135: 419. doi:10.1007/s00418-011-0797-z

Abstract

Myotonic dystrophies (DMs) are characterised by highly variable clinical manifestations consisting of muscle weakness and atrophy, and a wide spectrum of extramuscular manifestations. In both DM1 and DM2 forms, expanded nucleotide sequences cause the accumulation of mutant transcripts in the nucleus, thus deregulating the function of some RNA-binding proteins and providing a plausible explanation for the multifactorial phenotype of DM patients. However, at the skeletal muscle level, no mechanistic explanation for the muscle wasting has so far been proposed. We therefore performed a study in situ by immunoelectron microscopy on biceps brachii biopsies from DM1, DM2 and healthy subjects, providing the first ultrastructural evidence on the distribution of some nuclear ribonucleoprotein (RNP)-containing structures and molecular factors involved in pre-mRNA transcription and maturation in dystrophic myonuclei. Our results demonstrated an accumulation of splicing and cleavage factors in myonuclei of both DM1 and DM2 patients, suggesting an impairment of post-transcriptional pre-mRNA pathways. The transcription of the expanded sequences in DM myonuclei would therefore hamper functionality of the whole splicing machinery, slowing down the intranuclear molecular trafficking; this would reduce the capability of myonuclei to respond to anabolic stimuli thus contributing to muscle wasting.

Keywords

Myotonic dystrophySkeletal muscleRNA processingElectron microscopyImmunocytochemistry

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Manuela Malatesta
    • 1
  • Marzia Giagnacovo
    • 2
  • Rosanna Cardani
    • 3
    • 4
  • Giovanni Meola
    • 5
  • Carlo Pellicciari
    • 2
  1. 1.Dipartimento di Scienze Neurologiche, Neuropsicologiche, Morfologiche e Motorie, Sezione di Anatomia e IstologiaUniversità di VeronaVeronaItaly
  2. 2.Dipartimento di Biologia Animale, Laboratorio di Biologia cellulare e NeurobiologiaUniversità di PaviaPaviaItaly
  3. 3.Dipartimento di Biologia molecolare e BiotecnologieUniversità degli Studi di MilanoMilanItaly
  4. 4.Centro per lo Studio delle Malattie Neuromuscolari, CMNMilanItaly
  5. 5.Dipartimento di Neurologia, IRCCS Policlinico San DonatoUniversità degli Studi di MilanoMilanItaly