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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.

SUBMITTER: Nahand JS

PROVIDER: S-EPMC7412987 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Circular RNAs: New Epigenetic Signatures in Viral Infections.

Nahand Javid Sadri JS Jamshidi Sogol S Hamblin Michael R MR Mahjoubin-Tehran Maryam M Vosough Massoud M Jamali Marzieh M Khatami Alireza A Moghoofei Mohsen M Baghi Hossein Bannazadeh HB Mirzaei Hamed H

Frontiers in microbiology 20200731

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 suggeste ...[more]

PMID: 32849445

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Project description:Recent studies have identified circular RNAs (circRNAs) expressed from the Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV) human DNA tumor viruses. To gain initial insights into the potential relevance of EBV circRNAs in virus biology and disease, we assessed the circRNAome of the interspecies homologue rhesus macaque lymphocryptovirus (rLCV) in a naturally occurring lymphoma from a simian immunodeficiency virus (SIV)-infected rhesus macaque. This analysis revealed rLCV orthologues of the latency-associated EBV circular RNAs circRPMS1_E4_E3a and circEBNA_U. Also identified in two samples displaying unusually high lytic gene expression was a novel rLCV circRNA that contains both conserved and rLCV-specific RPMS1 exons and whose backsplice junctions flank an rLCV lytic origin of replication (OriLyt). Analysis of a lytic infection model for the murid herpesvirus 68 (MHV68) rhadinovirus identified a cluster of circRNAs near an MHV68 lytic origin of replication, with the most abundant of these, circM11_ORF69, spanning the OriLyt. Lastly, analysis of KSHV latency and reactivation models revealed the latency associated circRNA originating from the vIRF4 gene as the predominant viral circRNA. Together, the results of this study broaden our appreciation for circRNA repertoires in the Lymphocryptovirus and Rhadinovirus genera of gammaherpesviruses and provide evolutionary support for viral circRNA functions in latency and viral replication.IMPORTANCE Infection with oncogenic gammaherpesviruses leads to long-term viral persistence through a dynamic interplay between the virus and the host immune system. Critical for remodeling of the host cell environment after the immune responses are viral noncoding RNAs that modulate host signaling pathways without attracting adaptive immune recognition. Despite the importance of noncoding RNAs in persistent infection, the circRNA class of noncoding RNAs has only recently been identified in gammaherpesviruses. Accordingly, their roles in virus infection and associated oncogenesis are unknown. Here we report evolutionary conservation of EBV-encoded circRNAs determined by assessing the circRNAome in rLCV-infected lymphomas from an SIV-infected rhesus macaque, and we report latent and lytic circRNAs from KSHV and MHV68. These experiments demonstrate utilization of the circular RNA class of RNAs across 4 members of the gammaherpesvirus subfamily, and they identify orthologues and potential homoplastic circRNAs, implying conserved circRNA functions in virus biology and associated malignancies.

Dataset Information

Circular RNAs: New Epigenetic Signatures in Viral Infections.

Publications

Circular RNAs: New Epigenetic Signatures in Viral Infections.

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