Modulation of circRNA Metabolism by m6A Modification

Di Timoteo, G., Dattilo, D., Centron-Broco, A., Colantoni, A., Guarnacci, M., Rossi, F., Incarnato, D., Oliviero, S., Fatica, A., Morlando, M. & Bozzoni, I., 12-May-2020, In : Cell reports. 31, 6, 15 p., 107641.

Research output: Contribution to journalArticleAcademicpeer-review

  • Gaia Di Timoteo
  • Dario Dattilo
  • Alvaro Centron-Broco
  • Alessio Colantoni
  • Marco Guarnacci
  • Francesca Rossi
  • Danny Incarnato
  • Salvatore Oliviero
  • Alessandro Fatica
  • Mariangela Morlando
  • Irene Bozzoni

N6-methyladenosine (m6A) is an RNA modification well-known for its contribution to different processes controlling RNA metabolism, including splicing, stability, and translation of mRNA. Conversely, the role of m6A on the biogenesis and function of circular RNAs (circRNAs) has yet to be addressed. circRNAs belong to a class of covalently closed transcripts produced via a back-splicing reaction whereby a downstream 5' splice donor site fuses to an upstream 3' splice acceptor site. Starting from circ-ZNF609 as a study case, we discover that specific m6As control its accumulation and that METTL3 and YTHDC1 are required to direct the back-splicing reaction. This feature is shared with other circRNAs because we find a significant direct correlation among METTL3 requirement, YTHDC1 binding, and the ability of m6A exons to undergo back-splicing. Finally, because circ-ZNF609 displays the ability to be translated, we show that m6A modifications, through recognition by YTHDF3 and eIF4G2, modulate its translation.

Original languageEnglish
Article number107641
Number of pages15
JournalCell reports
Issue number6
Publication statusPublished - 12-May-2020



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