Abnormal Expression of RNA Polymerase II-associated Proteins in Muscle of Patients With Myofibrillar Myopathies

Histopathology. 2015 Dec;67(6):859-65. doi: 10.1111/his.12715. Epub 2015 May 25.

Abstract

Aims: Myofibrillar myopathies (MFMs) are a group of inherited or sporadic neuromuscular disorders characterized morphologically by foci of myofibril dissolution, disintegration of the Z-disk and insoluble protein aggregates within the muscle fibres. The sequential events leading to muscle fibre damage remains largely unknown.

Methods and results: We investigated the expression and the cellular localization of RNA polymerase II (RNAPII)-associated proteins (RPAPs) in muscle biopsies from patients with genetically proven and sporadic MFMs. Our data demonstrated that RPAP2, and to a lesser extent GPN1/RPAP4, are accumulated focally in the cytoplasm of MFM muscle fibres in which they co-localize with POLR2A/RPB1, the largest subunit of RNAPII, and correspond to αB-cystallin deposits in distribution and staining intensity. No abnormal staining for RPAP2 has been observed in muscle of patients with central cores, minicores and neurogenic target fibres.

Conclusions: Together, these findings could provide new insights into the molecular pathogenesis of MFMs and suggest that RPAP2 immunostaining can be a useful diagnostic tool to depict protein aggregates in MFMs.

Keywords: RNA polymerase II (RNAPII); RNA polymerase II associated proteins (RPAPs); myofibrillar myopathies; protein aggregates.

MeSH terms

  • Carrier Proteins / metabolism*
  • Female
  • Humans
  • Male
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Myopathies, Structural, Congenital / metabolism*
  • Myopathies, Structural, Congenital / pathology
  • RNA Polymerase II / metabolism*

Substances

  • Carrier Proteins
  • RPAP2 protein, human
  • RNA Polymerase II

Supplementary concepts

  • Myofibrillar Myopathy