TY - JOUR
T1 - Dysregulation of circular RNAs in myotonic dystrophy type 1
AU - Voellenkle, Christine
AU - Perfetti, Alessandra
AU - Carrara, Matteo
AU - Fuschi, Paola
AU - Renna, Laura Valentina
AU - Longo, Marialucia
AU - Sain, Simona Baghai
AU - Cardani, Rosanna
AU - Valaperta, Rea
AU - Silvestri, Gabriella
AU - Legnini, Ivano
AU - Bozzoni, Irene
AU - Furling, Denis
AU - Gaetano, Carlo
AU - Falcone, Germana
AU - Meola, Giovanni
AU - Martelli, Fabio
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Alternative splicing
KW - Circular RNA
KW - Muscular dystrophies
KW - Myotonic dystrophy
KW - Alternative splicing
KW - Circular RNA
KW - Muscular dystrophies
KW - Myotonic dystrophy
UR - http://hdl.handle.net/10807/166570
U2 - 10.3390/ijms20081938
DO - 10.3390/ijms20081938
M3 - Article
SN - 1661-6596
VL - 20
SP - 1938-N/A
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
ER -