Dysregulation of Circular RNAs in Myotonic Dystrophy Type 1

Int J Mol Sci. 2019 Apr 19;20(8):1938. doi: 10.3390/ijms20081938.


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.

Keywords: alternative splicing; circular RNA; muscular dystrophies.

MeSH terms

  • Adult
  • Alternative Splicing / genetics
  • Case-Control Studies
  • Cell Line
  • Female
  • Gene Expression Regulation*
  • Humans
  • Male
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Myotonic Dystrophy / blood
  • Myotonic Dystrophy / genetics*
  • Polymerase Chain Reaction
  • RNA / blood
  • RNA / genetics*
  • RNA, Circular
  • Reproducibility of Results


  • RNA, Circular
  • RNA