Circular RNA profiling reveals abundant and diverse circRNAs of SARS-CoV-2, SARS-CoV and MERS-CoV origin

Abstract

Circular RNAs (circRNAs) encoded by DNA genomes have been identified across host and pathogen species as parts of the transcriptome. Accumulating evidences indicate that circRNAs play critical roles in autoimmune diseases and viral pathogenesis. Here we report that RNA viruses of the Betacoronavirus genus of Coronaviridae, SARS-CoV-2, SARS-CoV and MERS-CoV, encode a novel type of circRNAs. Through de novo circRNA analyses of publicly available coronavirus-infection related deep RNA-Sequencing data, we identified 351, 224 and 2,764 circRNAs derived from SARS-CoV-2, SARS-CoV and MERS-CoV, respectively, and characterized two major back-splice events shared by these viruses. Coronavirus-derived circRNAs are more abundant and longer compared to host genome-derived circRNAs. Using a systematic strategy to amplify and identify back-splice junction sequences, we experimentally identified over 100 viral circRNAs from SARS-CoV-2 infected Vero E6 cells. This collection of circRNAs provided the first line of evidence for the abundance and diversity of coronavirus-derived circRNAs and suggested possible mechanisms driving circRNA biogenesis from RNA genomes. Our findings highlight circRNAs as an important component of the coronavirus transcriptome.SummaryWe report for the first time that abundant and diverse circRNAs are generated by SARS-CoV-2, SARS-CoV and MERS-CoV and represent a novel type of circRNAs that differ from circRNAs encoded by DNA genomes.

Circular RNAs Represent a Novel Class of Human Cytomegalovirus Transcripts

“…Recently, virus-encoded circRNAs were identified from infected cells. These viruses include KSHV, EBV, HPV, HBV, and coronaviruses ( 13 , 17 , 49 – 51 ). In the present study, we employed an unbiased algorithm, CIRI2, to analyze existing data sets to identify circRNAs not only for HCMV but also for EBV and KSHV.…”

“…Similar to our previously described method ( 49 , 55 ), the analysis was performed on two Intel W-3175× CPUs with 128 GB memory running on the Ubuntu system (version 18.04). The trimmed reads were aligned with the reference genomes of the TB40/E strain and HAN strain ( 24 ) using Python2 script ViReMa (–MicroInDel_Length 5 –Defuzz 0 -FuzzEntry).…”

Past, Present and Future: The Relationship Between Circular RNA and Immunity

“…CircRNAs, molecules closely associated with viral infection, is one option. A differential host circRNA expression profile analysis in human lung epithelial cells infected with SARS-CoV-2 was completed ( 64 ), and two circRNA profile analyses revealed abundant and diverse information regarding the identification and characterization of the circRNAs encoded by SARS-CoV-1, SARS-CoV-2 and MERS-CoV ( 65 , 66 ), facilitating future studies concerning on COVID-19 infection and pathogenesis. Arora et al.…”

Functional Roles of Non-coding RNAs in the Interaction Between Host and Influenza A Virus

“…Viral circRNAs have been identified in various classes of viruses including coronaviruses such as MERS-CoV, SARS-CoV-1, and SARS-CoV-2 (Yang et al, 2020;Cai et al, 2021), oncogenic viruses such as Epstein-Barr virus (EBV), Kaposi's sarcomaassociated herpesvirus (KSHV), human papillomavirus (HPV), etc. (Avilala et al, 2021;Tagawa et al, 2021), as well as IAVs.…”