Translation of circRNAs


  • N.R. Pamudurti
  • O. Bartok
  • M. Jens
  • R. Ashwal-Fluss
  • C. Stottmeister
  • L. Ruhe
  • M. Hanan
  • E. Wyler
  • D. Perez-Hernandez
  • E. Ramberger
  • S. Shenzis
  • M. Samson
  • G. Dittmar
  • M. Landthaler
  • M. Chekulaeva
  • N. Rajewsky
  • S. Kadener


  • Molecular Cell


  • Mol Cell 66 (1): 9-21


  • Circular RNAs (circRNAs) are abundant and evolutionarily conserved RNAs of largely unknown function. Here, we show that a subset of circRNAs is translated in vivo. By performing ribosome footprinting from fly heads, we demonstrate that a group of circRNAs is associated with translating ribosomes. Many of these ribo-circRNAs use the start codon of the hosting mRNA, are bound by membrane-associated ribosomes, and have evolutionarily conserved termination codons. In addition, we found that a circRNA generated from the muscleblind locus encodes a protein, which we detected in fly head extracts by mass spectrometry. Next, by performing in vivo and in vitro translation assays, we show that UTRs of ribo-circRNAs (cUTRs) allow cap-independent translation. Moreover, we found that starvation and FOXO likely regulate the translation of a circMbl isoform. Altogether, our study provides strong evidence for translation of circRNAs, revealing the existence of an unexplored layer of gene activity.