Sp1-Mediated circRNA circHipk2 Regulates Myogenesis by Targeting Ribosomal Protein Rpl7

Abstract

Circular RNAs (circRNAs) represent a class of covalently closed single-stranded RNA molecules that are emerging as essential regulators of various biological processes. The circRNA <i>circHipk2</i> originates from exon 2 of the <i>Hipk2</i> gene in mice and was reported to be involved in acute promyelocytic leukemia and myocardial injury. However, the functions and mechanisms of <i>circHipk2</i> in myogenesis are largely unknown. Here, to deepen our knowledge about the role of <i>circHipk2</i>, we studied the expression and function of <i>circHipk2</i> during skeletal myogenesis. We found that <i>circHipk2</i> was mostly distributed in the cytoplasm, and dynamically and differentially expressed in various myogenesis systems in vitro and in vivo. Functionally, overexpression of <i>circHipk2</i> inhibited myoblast proliferation and promoted myotube formation in C2C12 cells, whereas the opposite effects were observed after <i>circHipk2</i> knockdown. Mechanistically, <i>circHipk2</i> could directly bind to ribosomal protein Rpl7, an essential 60S preribosomal assembly factor, to inhibit ribosome translation. In addition, we verified that transcription factor <i>Sp1</i> directly bound to the promoter of <i>circHipk2</i> and affected the expression of <i>Hipk2</i> and <i>circHipk2</i> in C2C12 myoblasts. Collectively, these findings identify <i>circHipk2</i> as a candidate circRNA regulating ribosome biogenesis and myogenesis proliferation and differentiation.