Abnormal expression of RNA polymerase II-associated proteins in muscle of patients with myofibrillar myopathies

作者：Guglielmi Valeria; Marini Matteo; Masson Emilie Fiola; Malatesta Manuela; Forget Diane; Tomelleri Giuliano; Coulombe Benoit; Vattemi Gaetano^*

来源：Histopathology, 2015, 67(6): 859-865.

DOI：10.1111/his.12715

• myofibrillar myopathies
• protein aggregates
• RNA polymerase II (RNAPII)
• RNA polymerase II associated proteins (RPAPs)

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 alpha B-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.

• 出版日期2015-12