= Circular RNA
A <circular RNA> has a covalently closed <RNA> backbone with no free $5'$ or $3'$ end. The closure concerns the chain of <phosphodiester bonds>, not whether a drawing happens to look round. A linear <RNA> folded into a <stem-loop> still has two ends. Circular RNAs can arise through <RNA ligation>; some cellular examples are generated by <back-splicing> of transcribed sequences.<Purification and properties of bacteriophage T4-induced RNA ligase by R. Silber and others>[Abstract, intramolecular circularization]{ref}<Circular RNAs are abundant, conserved, and associated with ALU repeats by William R. Jeck and others>[Abstract and Figures1–4, endogenous backsplice products]{ref}
\Image[/circular-rna-backbone-topology.png]
{title=Backbone connectivity distinguishes <circular RNA> from folded linear <RNA>}
{description=Original eight-<nucleotide> schematic, not a molecular structure or folding prediction. Blue lines are covalent backbone links. The circle has eight links and no ends; either linear arrangement has seven links and two ends. Dashed contacts illustrate possible <base pairing> without joining the ends covalently. No particular sequence or geometric scale is specified.}
One internal cut in the circle produces a single linear chain. One internal cut in an already linear chain produces two fragments, assuming no other links hold the pieces together. This connectivity difference explains why enzymes requiring a free end can distinguish the molecules, although circularity does not make an RNA immune to every cleavage process.
A 2013 study combined <RNA sequencing> with and without treatment by <RNase R>, an enzyme acting from RNA ends. Enrichment of <back-splicing> junction reads, together with additional validation, supported a substantial population of endogenous circular molecules.<Circular RNAs are abundant, conserved, and associated with ALU repeats by William R. Jeck and others>[Figures1–4, matched treatment comparison and junction validation]{ref} Combining chemical resistance with junction evidence is more informative than classifying a molecule solely by its apparent shape or persistence after one treatment.
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