Efficient backsplicing produces translatable circular mRNAs

While the human transcriptome contains a large number of circular RNAs (circRNAs), the functions of most circRNAs remain unclear. Sequence annotation suggests that most circRNAs are generated from splicing in reversed orders across exons. However, the mechanisms of this backsplicing are largely unknown. Here we constructed a single exon minigene containing split GFP, and found that the pre-mRNA indeed produces circRNA through efficient backsplicing in human and Drosophila cells. The backsplicing is enhanced by complementary introns that form double-stranded RNA structure to bring splice sites in proximity, but such structure is not required. Moreover, backsplicing is regulated by general splicing factors and…

• NN
  National Natural Science Foundation of China

  Awards: 81422038, 31471235
• RP
  Recruitment Program of Global Experts
• NI
  National Institutes of Health

  Awards: CA158283, R01-CA158283