Circular RNAs (circRNAs) constitute a family of transcripts with unique 
structures and still largely unknown functions. Their biogenesis, which proceeds 
via a back-splicing reaction, is fairly well characterized, whereas their role 
in the modulation of physiologically relevant processes is still unclear. Here 
we performed expression profiling of circRNAs during in vitro differentiation of 
murine and human myoblasts, and we identified conserved species regulated in 
myogenesis and altered in Duchenne muscular dystrophy. A high-content functional 
genomic screen allowed the study of their functional role in muscle 
differentiation. One of them, circ-ZNF609, resulted in specifically controlling 
myoblast proliferation. Circ-ZNF609 contains an open reading frame spanning from 
the start codon, in common with the linear transcript, and terminating at an 
in-frame STOP codon, created upon circularization. Circ-ZNF609 is associated 
with heavy polysomes, and it is translated into a protein in a 
splicing-dependent and cap-independent manner, providing an example of a 
protein-coding circRNA in eukaryotes.