Circular RNAs Represent a Novel Class of Human Cytomegalovirus Transcripts

Yang, Shaomin; Liu, Xiaolian; Wang, Mei; Cao, Di; Jaijyan, Dabbu Kumar; Enescu, Nicole; Liu, Jian; Wu, Songbin; Wang, Sashuang; Sun, Wuping; Xiao, Lizu; Gu, Alison; Zhou, Hong; Tyagi, Sanjay; Wu, Jianguo; Tang, Qiyi; Zhu, Hua

doi:10.1128/spectrum.01106-22

Cited by 15 publications

(16 citation statements)

References 64 publications

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“…CircRNAs are an alternative splicing product and thus expand the number of transcripts without extending genome size; a strategy that may be advantageous for organisms with limited coding space. In line with this hypothesis, recent studies have experimentally confirmed viral circRNAs expressed by beta-and gamma-herpesviruses, human papillomavirus, Merkel cell polyomavirus, hepatitis B virus, respiratory syncytial virus, and coronaviruses; with bioinformatic evidence for many other viruses (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 78%

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Noncanonical circRNA biogenesis driven by alpha and gamma herpesviruses

Dremel

Kopardé

Arbuckle

et al. 2022

Preprint

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Herpesviruses express over 100 transcripts, including messenger RNAs, long noncoding RNAs, and microRNAs. Herein, we add to this list by performing circular RNA (circRNA) profiling for Herpes Simplex Virus-1, Kaposi sarcoma-associated herpesvirus (KSHV), and murine gammaherpesvirus 68. Using cell culture and animal models of lytic and latent infection, we identified thousands of back-splicing variants. This included circRNAs derived from viral latency genes (circK12, circLAT). During lytic infection circRNAs tiled the viral genome, with a transcriptional density 4,500-fold greater than the host. We characterized cis- and trans-elements controlling back-splicing and found that lytic infection promoted rampant, sequence-independent back-splicing. Using eCLIP and 4SU-Sequencing, we determined that the KSHV RNA binding protein (ORF57) preferentially bound viral circRNAs and globally promoted accumulation post-transcriptionally. Our work elucidates a unique splicing mechanism driven by late lytic replication and identifies a class of transcripts with potential to function in replication, persistence, or tumorigenesis.

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Section: Introductionmentioning

confidence: 78%

“…Since circRNAs lack 5' and 3' ends they have low immunogenicity and extended halflives that average ~2.5 times longer than their linear counterparts (14,26). CircRNAs generally function to regulate gene expression.…”

Section: Introductionmentioning

confidence: 99%

Noncanonical circRNA biogenesis driven by alpha and gamma herpesviruses

Dremel

Kopardé

Arbuckle

et al. 2022

Preprint

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“…A newly published work by Yang et al. biomatically predicts HCMV-encoded circRNAs based on transcriptomic data from NCBI GEO database and validate viral circRNA expressions in cells infected by different clinical HCMV strains (TB40/E, Towne and Toledo, respectively) ( Yang et al., 2022 ). Their results suggest that the expression patterns of HCMV circRNAs are different between different strains and cell lines.…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of human cytomegalovirus-encoded circular RNAs

Jing-yi

Wang

Zhang

et al. 2022

Front. Cell. Infect. Microbiol.

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Circular RNA (circRNA) exists extensively and plays essential roles in serving as microRNA (miRNA) or protein sponges and protein scaffolding in many organisms. However, the profiles and potential functions of the virus-encoded circRNA, including human cytomegalovirus (HCMV)-encoded circular RNAs, remain unclear. In the present study, HCMV-encoded circRNAs profile in human embryonic lung fibroblasts (HELF) with lytic infection was investigated using RNA deep sequencing and bioinformatics analysis. In total, 629 HCMV-encoded circRNAs were identified with various expression patterns in our results. The full sequences and alternative splicings of circUS12, circUL55, and circUL89 were verified by reverse transcriptase-PCR (RT-PCR) with divergent primers followed and Sanger sequencing. Transcription of circUL89 was validated by Northern blot. The HCMV-encoded circRNA-miRNA network analyses revealed the potential function of HCMV-encoded circRNAs during HCMV infection in HELFs. Collectively, HCMV infection deduced abundant HCMV-associated circRNAs during infection, and the HCMV-encoded circRNAs might play important roles in benefiting HCMV infection.

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“…It has been reported that circRNA plays important biological functions including microRNA (miRNA) sponges, parental gene expression regulators, and the translation template ( 2 – 5 ). Viral circRNAs have been recently identified from cells infected with different DNA viruses, such as Epstein-Barr virus (EBV) ( 6 , 7 ), Kaposi’s sarcoma-associated herpesvirus (KSHV) ( 8 ), human papillomaviruses (HPVs) ( 9 ), and human cytomegalovirus (HCMV) ( 10 ). Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic and poses a high threat to global health.…”

Section: Lettermentioning

confidence: 99%