Circular RNA Pde4dip regulates myogenesis by interacting with Zfp143 mRNA: A novel regulatory axis

Abstract Many transcriptional and post-transcriptional regulators tightly regulate skeletal muscle myogenesis, including recently discovered circular RNAs (circRNAs). In this study, we used a crosslinking-based sequencing method called CliPP-Seq, wherein we performed AMT-mediated Cross-Linking of RNA-RNA duplexes followed by Poly-A RNA Pulldown and sequencing to identify mRNA-interacting circRNAs in the mRNA samples of mouse C2C12 myoblasts and myotubes. BLAST analysis of the circRNAs with mRNAs identified their potential interacting partners. Interestingly, silencing of the circular RNA Pde4dip (circPde4dip) altered the target mRNA Zfp143 (zinc finger protein 143) expression and suppressed the differentiation of C2C12 myoblasts into myotubes. In summary, we identified unexplored mRNA-interacting circRNAs and their possible role in muscle cell differentiation, specifically the circPde4dip-Zfp143 mRNA interaction as one of the key regulators of myogenesis. Highlights Identified mRNA-associated circRNAs in differentiating C2C12 myoblasts The first report identifying the regulation of myogenesis by circRNA-mRNA interaction circPde4dip regulates C2C12 differentiation by interacting with Zfp143 mRNA Competing Interest Statement Amaresh C. Panda is a non-executive director and co-founder of RNA Biotech Pvt., Ltd. The remaining authors declare no conflicts of interest.