Circular RNAs are abundant, conserved, and associated with ALU repeats

• DOI: 10.1261/rna.035667.112
• Publication Date: 2012-12-19T04:04:51Z
• Authors: William R. Jeck; Jessica A. Sorren...; Kai Wang; Michael K. Slevin; Christin E. Burd; Jinze Liu; William F. Marzluff; Norman E. Sharpless
• Keywords: Circular RNA; Small nucleolar RNA; Alu element; RNA Silencing

Circular RNAs composed of exonic sequence have been described in a small number genes. Thought to result from splicing errors, circular RNA species possess no known function. To delineate the universe endogenous RNAs, we performed high-throughput sequencing (RNA-seq) libraries prepared ribosome-depleted with or without digestion exonuclease, RNase R. We identified >25,000 distinct human fibroblasts that contained non-colinear exons (a “backsplice”) and were reproducibly enriched by exonuclease degradation linear RNA. These validated as (ecircRNA), rather than RNA, more stable associated mRNAs vivo. In some cases, abundance molecules exceeded mRNA >10-fold. By conservative estimate, ecircRNAs 14.4% actively transcribed genes fibroblasts. Application this method murine testis 69 precisely orthologous locations RNAs. Of note, paralogous kinases HIPK2 HIPK3 produce abundant ecircRNA their second exon both humans mice. Though contain an AUG translation start, it other not bound ribosomes. could be degraded siRNAs and, therefore, may act competing Bioinformatic analysis revealed shared features circularized exons, including long bordering introns complementary ALU repeats. data show are abundant, stable, conserved nonrandom products involved control gene expression.