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    A brief history of circular RNAs (CircRNAs)

  • Maliheh Hosseinpour,1,*
    1. M.Sc; Molecular Genetic; Department of Biology, Faculty of Sciences, Arak University, Arak, Iran


  • Introduction: The concept of circular RNAs (circRNAs) was first proposed in 1976 by Sanger et al. They attempted to understand how viroids act as plant pathogens. They studied four diverse purified viroids and explained that RNA molecules in viroids are unable to be labeled at the ends of 5՜ and 3՜ and they tolled viroids are covalently connected circular RNA molecules. CircRNAs were discovered in mammals in 1991. Comprehensive research on circRNAs started with the discovery of large amounts of circRNAs in human cells in 2012. Compared with conventional linear RNA, the end of 5՜-3՜ in circRNAs are covalently closed, so circRNAs, in order to maintain stability, do not need a cap and poly-A tail at their 5՜ and 3՜ ends. CircRNAs have higher stability, especially against degradation of exonucleases, which is a structural advantage for them. CircRNAs are found in all branches of life, for example as the genome of viroid plant pathogens and hepatitis delta virus (HDV) or appear as rRNA introns, spliced tRNAs, and mediators of rRNA processing in the archaea. In addition, circRNAs are found within the life cycle of group I eukaryotic and bacterial introns. CircRNAs are categorized as exonic (ecircRNA), exon-intron (EIcircRNA), or intronic (ciRNA). CircRNAs may stay within the nucleus or enter the cytoplasm. CircRNAs make it possible to replicate within the form of a rolling circle. Although most circRNAs contain exons of protein-coding genes, circRNAs can also originate from introns, intergenic regions, UTRs, ncRNA loci, and antisense sites with known transcripts.
  • Methods: This study has performed by searching the “PubMed database” and “Google scholar” by different combinations of terms “circRNA” and “history of circular RNAs”. The concept of the RNA circle was investigated.
  • Results: Studies have shown that the aberrant expression of cyclic RNA plays a vital role in the progression of various human diseases. RNA circles represent a powerful tool in future biotechnology and gene transfer research for the development of new gene therapies.
  • Conclusion: CircRNAs have great potential and there is still a lot of unknown about circRNAs. With the persistent efforts in this field, circRNAs will play a basic role in research and medical applications and become an important part of human health shortly.
  • Keywords: CircRNA, Circular RNA, RNA synthesis, Splicing.