An Investigation of Circular RNAs on a Genome-Wide Scale

An Investigation of Circular RNAs on a Genome-Wide Scale Public Deposited

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Abstract

The genome communicates genetic information to the cell through the process of transcription. This yields diverse products, which are then further altered by post-translational processing. Circular RNAs with no free 3' or 5' end were previously thought to be rare products of this post-translational processing. It has recently become appreciated that exonic circular RNAs (ecircRNAs) are common products of some genes, and can be functional. In addition to their functional roles, ecircRNA formation may have critical consequences to their source pre-mRNA transcripts. We recently identified abundant ecircRNA production in a locus linked to numerous human diseases, the ANRIL gene in the INK4/ARF locus. A meta-analysis of genome wide association studies revealed that this locus was a significant predictor of at least 10 distinct diseases, outstripping all genomic regions but the major histocompatibility locus. To fully characterize ecircRNA transcription products of INK4/ARF and ecircRNA production genome wide, we developed a coupled biochemical enrichment and bioinformatic technique. Genome wide ecircRNAs were observed to be cytoplasmic, highly stable, and the most abundant products of some genes. While ecircRNAs were not polysome associated, they were targeted by siRNAs, suggesting a role as RNA sponges. We further identified genomic features that likely contribute to ecircRNA production. This method offers new insights into ecircRNA formation and function in the cell.

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