Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis

Mol Cell. 2017 Apr 6;66(1):22-37.e9. doi: 10.1016/j.molcel.2017.02.017. Epub 2017 Mar 23.

Abstract

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.

Keywords: DMD; cap independent; circRNA; circular RNA; muscle differentiation; myogenesis; non-coding RNA; proliferation; translation.

MeSH terms

  • Animals
  • Cell Proliferation*
  • Genotype
  • HeLa Cells
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Mice
  • Muscle Development*
  • Muscle Proteins / biosynthesis*
  • Muscle Proteins / genetics
  • Muscular Dystrophy, Duchenne / genetics
  • Muscular Dystrophy, Duchenne / metabolism*
  • Muscular Dystrophy, Duchenne / pathology
  • Muscular Dystrophy, Duchenne / physiopathology
  • Myoblasts, Skeletal / metabolism*
  • Myoblasts, Skeletal / pathology
  • Open Reading Frames
  • Phenotype
  • Protein Biosynthesis*
  • RNA / genetics
  • RNA / metabolism*
  • RNA Caps / genetics
  • RNA Caps / metabolism
  • RNA Interference
  • RNA Splicing
  • RNA, Circular
  • Sequence Analysis, RNA / methods
  • Signal Transduction
  • Transfection

Substances

  • Muscle Proteins
  • RNA Caps
  • RNA, Circular
  • RNA