Functions and Implications of Circular RNAs in Antiviral Immunity

Abstract

In addition to mature mRNAs, splicing of pol II transcripts generates numerous other RNAs including circular RNAs (circRNAs). circRNAs are a group of transcripts generated by non-sequential back splicing or forward splicing of exons, introns or a combination of both from a donor to an acceptor target. This forms covalently closed RNA molecule i.e. without free 5' end caps or 3' Poly (A) tails thereby making them more stable than their linear counterparts. Though they are recognized as part of non-coding RNAs, long noncoding precisely; evidence of translations has been reported from these molecules. circRNAs are considered emerging new members of the gene regulatory family. These circRNAs have several potential modes of action, some of which serve as microRNAs sponges shown in Table 1, protein binding RNAs, cellular transports, transcriptional regulators and modulating immune system. Viral circRNAs may evade immune recognition by many proposed mechanisms. These include undergoing slicing by host splicing machinery, being single stranded lacking free 5' and 3' ends, having miRNA sponge function, convenient regulatory functions which include initiating lytic replication, etc. Pattern of expression of these circRNAs differs from healthy individuals to different stages of viral infectious diseases. Thus, their use as potential biomarkers for diagnostics and future therapeutics targets have been proposed, especially with regards to viral infections that seem impossible for the human immune system to totally eliminate like the Epstein-Barr viral infection. So, this review summarizes the functions and implications of circRNAs regarding antiviral immunity.