2. Academic Validation
  3. Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis

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.
Ivano Legnini 1,  Gaia Di Timoteo 1,  Francesca Rossi 1,  Mariangela Morlando 1,  Francesca Briganti 1,  Olga Sthandier 1,  Alessandro Fatica 1,  Tiziana Santini 2,  Adrian Andronache 3,  Mark Wade 3,  Pietro Laneve 2,  Nikolaus Rajewsky 4,  Irene Bozzoni 5
Affiliations

Affiliations

  • 1 Department of Biology and Biotechnology Charles Darwin and IBPM, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
  • 2 Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy.
  • 3 Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Via Adamello 16, 20139 Milan, Italy.
  • 4 Berlin Institute for Medical Systems Biology, Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
  • 5 Department of Biology and Biotechnology Charles Darwin and IBPM, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy; Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy; Institut Pasteur Italy, Fondazione Cenci-Bolognetti, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy. Electronic address: irene.bozzoni@uniroma1.it.
PMID: 28344082 DOI: 10.1016/j.molcel.2017.02.017
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.

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