Translation of CircRNAs.

April 06, 2017 By:
  • Pamudurti NR
  • Bartok O
  • Jens M
  • Ashwal-Fluss R
  • Stottmeister C
  • Ruhe L
  • Hanan M
  • Wyler E
  • Perez-Hernandez D
  • Ramberger E
  • Shenzis S
  • Samson M
  • Dittmar G
  • Landthaler M
  • Chekulaeva M
  • Rajewsky N
  • Kadener S.

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.

2017 Apr. Mol Cell.66(1):9-21 e7. Epub 2017 Mar 23.
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