Circular RNAs: New Epigenetic Signatures in Viral Infections

Abstract

Covalent closed circular RNAs (circRNAs) can act as a bridge between non-coding RNAs and coding messenger RNAs. CircRNAs are generated by a back-splicing mechanism during post-transcriptional processing and are abundantly expressed in eukaryotic cells. CircRNAs can act via the modulation of RNA transcription and protein production, and by the sponging of microRNAs (miRNAs). CircRNAs are now thought to be involved in many different biological and pathological processes. Some studies have suggested that the expression of host circRNAs is dysregulated in several types of virus-infected cells, compared to control cells. It is highly likely that viruses can use these molecules for their own purposes. In addition, some viral genes are able to produce viral circRNAs (VcircRNA) by a back-splicing mechanism. However, the viral genes that encode VcircRNAs, and their functions, are poorly studied. In this review, we highlight some new findings about the interaction of host circRNAs and viral infection. Moreover, the potential of VcircRNAs derived from the virus itself, to act as biomarkers and therapeutic targets is summarized.

Keywords: VcircRNA; back-splicing; biomarker; circular RNA; epigenetics; viral infection.

FIGURE 1

Biogenesis of circRNAs. Pre-mRNA can be processed through either canonical splicing to produce linear RNAs (left) or backsplicing to generate circRNAs (right). CircRNAs are mainly divided into three categories based on their components. Exonic circRNAs (ecircRNAs) are exclusively composed of exons and represent the largest group of circRNAs, intronic circRNA (ciRNA) are exclusively composed of introns, and exon-intron circRNA (elciRNA) are exon-intron sequences. In this figure, arrows show the splicing events for generating the products, blue lines show introns, and colored lines (red/yellow) show exons.

FIGURE 2

Schematic of circRNA functions. CircRNAs might function as miRNA sponges by competing for the binding of miRNA sequences, lessening the impact of miRNA-mediated regulation of gene expression. CircRNAs might function as protein sponges. Some circRNAs might control the expression of proteins by sequestering mRNA translation start sites. CircRNAs might be translated to create functional proteins.

FIGURE 3

Formation and function of ebv-circRPMS1in EBV-infected NPC cells. Genomic location of the RPMS1 gene in EBV-BART region and ebv-circRPMS1 that originated from exon 2–4 of the RPMS1 gene by back-splicing. CircRPMS1 may be involved in the oncogenesis of NPC via sponging of miR-31, miR-451, and miR-203.