A circular ribo-oligonucleotide or RNA is a noncoding RNA
Circular RNAs (circRNAs), or circular ribo-oligonucleotides, were recently added to the growing list of noncoding RNAs. However, since the last 20 years circular RNAs were known to biologists. These types of molecules were thought to be artefacts or molecular flukes resulting from aberrant RNA splicing or from the infection of host genes by specific pathogens. In the early years circular RNAs were found in plant viroids and the hepatitis δ virus. More recently circular RNAs have been detected in animal cells as well. However, their function was unclear.
Recent findings from the laboratories of Nikolaus Rajewsky and Jørgen Kjems have now defined a function for one circular RNA that binds the microRNA miR-7. Their results indicated that this circular RNA is full of microRNA binding sites. Apparently this circular RNA can act as a miRNA 'sponge' capable of binding many miRNAs per circular RNA molecule. In addition, their results suggested a role for circular RNAs in post-transcriptional regulation.
More resently, in 2012, Salzman et al. reported that circular RNA isoforms are a prevalent feature of eukaryotic gene expression programs. Previously thought to be very rare, these observations suggested that the major RNA isoform from hundreds of human genes are circular RNAs. In the following year, in 2013, Salzman et al. used an improved computational approach for the identification of circular RNA. This new method allowed the scientists to detect a more extensive catalogue of circular RNA. Many, many more than previously reported. This also included small RNA circles formed by non-canonical splicing of short exons and noncoding RNAs. The research group found that the expression of circular RNAs in Drosophila melanogaster is widespread. In addition, the researchers estimated that in humans, circular RNAs may account for approximately 1%. That is as many molecules as poly(A) RNA. Furthermore, the researchers suggested that this newly found abundance of circular RNA could significantly alter our present perspective on post-transcriptional regulation as well as the roles that RNA can play in the cell.
The improved detection of circular RNA isoforms allowed the scientists to characterize how many of differential circular RNA splicing events happen within a single gene and also to study variations in alternative splicing of circular RNAs. These observations support the hypothesis that circular RNAs may have an evolutionarily conserved function. However, their exact nature and mechanisms are still to be discovered.
Already a database for circular RNAs is available for browsing and downloading information and the location on the chromosomes of identified circular RNAs: Cirbase.
Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J. Natural RNA circles function as efficient microRNA sponges. Nature. 2013 Mar 21;495(7441):384-8. [PubMed]
Jeck WR, Sharpless NE. Detecting and characterizing circular RNAs. Nat Biotechnol. 2014 May;32(5):453-61. [PMC]
Kos, A., Dijkema, R., Arnberg, A.C., van der Meide, P.H. & Schellekens, H. The hepatitis delta (delta) virus possesses a circular RNA. Nature 323, 558–560 (1986). [PubMed]
Sebastian Memczak, Marvin Jens, Antigoni Elefsinioti, Francesca Torti, Janna Krueger,Agnieszka Rybak, Luisa Maier, Sebastian D. Mackowiak, Lea H. Gregersen, Mathias Munschauer, Alexander Loewer, Ulrike Ziebold, Markus Landthaler, Christine Kocks,Ferdinand le Noble & Nikolaus Rajewsky; Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495, 333–338. [Nature]
Mohan T. Bolisetty1 and Brenton R. Graveley1; Circuitous Route to Transcription Regulation. Molecular Cell 51, September 26, 2013, pp 705-706. [PMC]
Sanger, H.L., Klotz, G., Riesner, D., Gross, H.J. & Kleinschmidt, A.K.; Viroids are single-stranded covalently closed circular RNA molecules existing as highly basepaired rod-like structures. Proc. Natl. Acad. Sci. USA 73, 3852–3856 (1976). [PMC]
Salzman J, Gawad C, Wang PL, Lacayo N, Brown PO (2012) Circular RNAs Are the Predominant Transcript Isoform from Hundreds of Human Genes in Diverse Cell Types. PLoS ONE 7(2): e30733. [PMC]