
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.
RNA Caps, Cancer Research, Genotype, Codon, Initiator, Nutritional Status, Article, Mass Spectrometry, Cell Line, Mice, Animals, Drosophila Proteins, Molecular Biology, Nuclear Proteins, Forkhead Transcription Factors, Cell Biology, RNA, Circular, Drosophila melanogaster, Phenotype, Cardiovascular and Metabolic Diseases, Protein Biosynthesis, Mutation, Codon, Terminator, Nucleic Acid Conformation, RNA, Technology Platforms, Function and Dysfunction of the Nervous System, Head
RNA Caps, Cancer Research, Genotype, Codon, Initiator, Nutritional Status, Article, Mass Spectrometry, Cell Line, Mice, Animals, Drosophila Proteins, Molecular Biology, Nuclear Proteins, Forkhead Transcription Factors, Cell Biology, RNA, Circular, Drosophila melanogaster, Phenotype, Cardiovascular and Metabolic Diseases, Protein Biosynthesis, Mutation, Codon, Terminator, Nucleic Acid Conformation, RNA, Technology Platforms, Function and Dysfunction of the Nervous System, Head
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