Molecular Cell
Volume 66, Issue 1, 6 April 2017, Pages 9-21.e7
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Article
Translation of CircRNAs

https://doi.org/10.1016/j.molcel.2017.02.021Get rights and content
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Highlights

  • Specific circRNAs are associated with translating ribosomes

  • Ribosome footprinting reads match termination codon signature for circMbl

  • circMbl3-derived protein is detected by mass spectrometry

  • circRNAs are translated in vitro and in vivo in a cap-independent manner

Summary

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.

Keywords

circRNA
translation
muscleblind
cap-independent

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