RNA processing is altered in skeletal muscle nuclei of patients affected by myotonic dystrophy
Articolo
Data di Pubblicazione:
2011
Citazione:
RNA processing is altered in skeletal muscle nuclei of patients affected by myotonic dystrophy / M. Malatesta, M. Giagnacovo, R. Cardani, G. Meola, C. Pellicciari. - In: HISTOCHEMISTRY AND CELL BIOLOGY. - ISSN 0948-6143. - 135:4(2011 Apr), pp. 419-425.
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
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Electron microscopy; Immunocytochemistry; Myotonic dystrophy; RNA processing; Skeletal muscle
Elenco autori:
M. Malatesta, M. Giagnacovo, R. Cardani, G. Meola, C. Pellicciari
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