Translation of CircRNAs

Mol Cell. 2017 Apr 6;66(1):9-21.e7. doi: 10.1016/j.molcel.2017.02.021. Epub 2017 Mar 23.

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.

Keywords: cap-independent; circRNA; muscleblind; translation.

MeSH terms

  • Animals
  • Cell Line
  • Codon, Initiator
  • Codon, Terminator
  • Drosophila Proteins / biosynthesis*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Forkhead Transcription Factors / metabolism
  • Genotype
  • Head
  • Mass Spectrometry
  • Mice
  • Mutation
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • Nucleic Acid Conformation
  • Nutritional Status
  • Phenotype
  • Protein Biosynthesis*
  • RNA / chemistry
  • RNA / genetics
  • RNA / metabolism*
  • RNA Caps / chemistry
  • RNA Caps / genetics
  • RNA, Circular
  • Rats
  • Ribosomes / chemistry
  • Ribosomes / genetics
  • Ribosomes / metabolism*
  • Starvation / genetics
  • Starvation / metabolism
  • Structure-Activity Relationship
  • Transfection

Substances

  • Codon, Initiator
  • Codon, Terminator
  • Drosophila Proteins
  • FOXO protein, Drosophila
  • Forkhead Transcription Factors
  • Nuclear Proteins
  • RNA Caps
  • RNA, Circular
  • mbl protein, Drosophila
  • RNA