SURVEY AND SUMMARY RNA circularization strategies in vivo and in vitro

In the plenitude of naturally occurring RNAs, circular RNAs (circRNAs) and their biological role were un-derestimated for years. However, circRNAs are ubiq-uitous in all domains of life, including eukaryotes, archaea, bacteria and viruses, where they can ful-fill diverse biological functions. Some of those func-tions, as for example playing a role in the life cy-cle of viral and viroid genomes or in the maturation of tRNA genes, have been elucidated; other putative functions still remain elusive. Due to the resistance to exonucleases, circRNAs are promising tools for in vivo application as aptamers, trans-cleaving ri-bozymes or siRNAs. How are circRNAs generated in vivo and what approaches do exist to produce ring-shaped RNAs in vitro? In this review we illustrate the occurrence and mechanisms of RNA circularization in vivo, survey methods for the generation of circRNA in vitro and provide appropriate protocols