Dysregulation of circular RNAs in myotonic dystrophy type 1

Christine Voellenkle, Alessandra Perfetti, Matteo Carrara, Paola Fuschi, Laura Valentina Renna, Marialucia Longo, Simona Baghai Sain, Rosanna Cardani, Rea Valaperta, Gabriella Silvestri, Ivano Legnini, Irene Bozzoni, Denis Furling, Carlo Gaetano, Germana Falcone, Giovanni Meola, Fabio Martelli

Research output: Contribution to journalArticle


Circular RNAs (circRNAs) constitute a recently re-discovered class of non-coding RNAs functioning as sponges for miRNAs and proteins, affecting RNA splicing and regulating transcription. CircRNAs are generated by “back-splicing”, which is the linking covalently of 3′- and 5′-ends of exons. Thus, circRNA levels might be deregulated in conditions associated with altered RNA-splicing. Significantly, growing evidence indicates their role in human diseases. Specifically, myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by expanded CTG repeats in the DMPK gene which results in abnormal mRNA-splicing. In this investigation, circRNAs expressed in DM1 skeletal muscles were identified by analyzing RNA-sequencing data-sets followed by qPCR validation. In muscle biopsies, out of nine tested, four transcripts showed an increased circular fraction: CDYL, HIPK3, RTN4_03, and ZNF609. Their circular fraction values correlated with skeletal muscle strength and with splicing biomarkers of disease severity, and displayed higher values in more severely affected patients. Moreover, Receiver-Operating-Characteristics curves of these four circRNAs discriminated DM1 patients from controls. The identified circRNAs were also detectable in peripheral-blood-mononuclear-cells (PBMCs) and the plasma of DM1 patients, but they were not regulated significantly. Finally, increased circular fractions of RTN4_03 and ZNF609 were also observed in differentiated myogenic cell lines derived from DM1 patients. In conclusion, this pilot study identified circRNA dysregulation in DM1 patients.

Original languageEnglish
Article number1938
JournalInternational Journal of Molecular Sciences
Issue number8
Publication statusPublished - Apr 2 2019


  • Alternative splicing
  • Circular RNA
  • Muscular dystrophies

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint Dive into the research topics of 'Dysregulation of circular RNAs in myotonic dystrophy type 1'. Together they form a unique fingerprint.

  • Cite this