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

Manuela Malatesta, Marzia Giagnacovo, Rosanna Cardani, Giovanni Meola, Carlo Pellicciari

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)419-425
Number of pages7
JournalHistochemistry and Cell Biology
Volume135
Issue number4
DOIs
Publication statusPublished - Apr 2011

Fingerprint

Myotonic Dystrophy
RNA Precursors
Skeletal Muscle
RNA
Muscles
Ribonucleoproteins
RNA-Binding Proteins
Muscular Atrophy
Immunoelectron Microscopy
Muscle Weakness
Molecular Structure
Healthy Volunteers
Phenotype
Biopsy
RNA Splicing Factors

Keywords

  • Electron microscopy
  • Immunocytochemistry
  • Myotonic dystrophy
  • RNA processing
  • Skeletal muscle

ASJC Scopus subject areas

  • Cell Biology
  • Histology
  • Medical Laboratory Technology
  • Molecular Biology

Cite this

RNA processing is altered in skeletal muscle nuclei of patients affected by myotonic dystrophy. / Malatesta, Manuela; Giagnacovo, Marzia; Cardani, Rosanna; Meola, Giovanni; Pellicciari, Carlo.

In: Histochemistry and Cell Biology, Vol. 135, No. 4, 04.2011, p. 419-425.

Research output: Contribution to journalArticle

Malatesta, Manuela ; Giagnacovo, Marzia ; Cardani, Rosanna ; Meola, Giovanni ; Pellicciari, Carlo. / RNA processing is altered in skeletal muscle nuclei of patients affected by myotonic dystrophy. In: Histochemistry and Cell Biology. 2011 ; Vol. 135, No. 4. pp. 419-425.
@article{874c834d269e40b4b407d45c212486b1,
title = "RNA processing is altered in skeletal muscle nuclei of patients affected by myotonic dystrophy",
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 = "Electron microscopy, Immunocytochemistry, Myotonic dystrophy, RNA processing, Skeletal muscle",
author = "Manuela Malatesta and Marzia Giagnacovo and Rosanna Cardani and Giovanni Meola and Carlo Pellicciari",
year = "2011",
month = "4",
doi = "10.1007/s00418-011-0797-z",
language = "English",
volume = "135",
pages = "419--425",
journal = "Histochemistry and Cell Biology",
issn = "0948-6143",
publisher = "Springer Verlag",
number = "4",

}

TY - JOUR

T1 - RNA processing is altered in skeletal muscle nuclei of patients affected by myotonic dystrophy

AU - Malatesta, Manuela

AU - Giagnacovo, Marzia

AU - Cardani, Rosanna

AU - Meola, Giovanni

AU - Pellicciari, Carlo

PY - 2011/4

Y1 - 2011/4

N2 - 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.

AB - 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.

KW - Electron microscopy

KW - Immunocytochemistry

KW - Myotonic dystrophy

KW - RNA processing

KW - Skeletal muscle

UR - http://www.scopus.com/inward/record.url?scp=79956224888&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79956224888&partnerID=8YFLogxK

U2 - 10.1007/s00418-011-0797-z

DO - 10.1007/s00418-011-0797-z

M3 - Article

C2 - 21387185

AN - SCOPUS:79956224888

VL - 135

SP - 419

EP - 425

JO - Histochemistry and Cell Biology

JF - Histochemistry and Cell Biology

SN - 0948-6143

IS - 4

ER -