Translation of CircRNAs

Nagarjuna Reddy Pamudurti, Osnat Bartok, Marvin Jens, Reut Ashwal-Fluss, Christin Stottmeister, Larissa Ruhe, Mor Hanan, Emanuel Wyler, Daniel Perez-Hernandez, Evelyn Ramberger, Shlomo Shenzis, Moshe Samson, Gunnar Dittmar, Markus Landthaler, Marina Chekulaeva, Nikolaus Rajewsky, Sebastian Kadener*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

1001 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)9-21.e7
JournalMolecular Cell
Volume66
Issue number1
DOIs
Publication statusPublished - 6 Apr 2017
Externally publishedYes

Keywords

  • cap-independent
  • circRNA
  • muscleblind
  • translation

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