The emerging regulatory mechanisms and biological function of circular RNAs in skeletal muscle development

Circular RNAs (circRNAs) are novel noncoding RNAs that assume a covalently closed-loop structure. Because of technical limitations in research, circRNAs were long considered to be byproducts of the RNA splicing process. Recently, emerging evidence has indicated that circRNAs can regulate gene expression by sponging microRNAs (miRNAs) or proteins, functioning as protein scaffolds, regulating transcription and splicing, and acting as templates for translation, thereby extending the functional complexity and diversity of eukaryotic transcriptomes. Remarkably, an increasing number of studies have revealed that circRNAs are stable, evolutionarily conserved, and are often expressed in a tissue- or developmental stage-specific patterns, especially abundant in muscle tissue. circRNAs are emerging as powerful regulators in diverse cellular processes and diseases, particularly in skeletal muscle myogenesis. Here, we describe circRNAs discovery, classification, and regulatory mechanisms, highlight the current understanding of circRNAs in regulating skeletal muscle development, and tell the story of how circRNAs, once thought to be “splicing noise”, have become “genetic treasures”. [Display omitted] •circRNAs can regulate transcription, affect splicing and act as templates for translation.•circRNAs are emerging as powerful regulators in skeletal muscle myogenesis.•We describe the discovery, classification, and regulatory mechanisms of circRNAs.