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Translation of CircRNAs #MMPMID28344080
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
Mol Cell 2017[Apr]; 66 (1): 9-21.e7 PMID28344080show ga
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.