Identification and characterization of a novel Epstein-Barr Virus-encoded circular RNA from LMP-2 Gene

Tan, Ke-En and Ng, Wei Lun and Marinov, Georgi K. and Yu, Ken Hung-On and Tan, Lu Ping and Liau, Ee Shan and Goh, Sook Yan and Yeo, Kok Siong and Yip, Kevin Y. and Lo, Kwok-Wai and Khoo, Alan Soo-Beng and Yap, Lee-Fah and Ea, Chee-Kwee and Lim, Yat-Yuen (2021) Identification and characterization of a novel Epstein-Barr Virus-encoded circular RNA from LMP-2 Gene. Scientific Reports, 11 (1). ISSN 2045-2322, DOI

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Epstein-Barr virus (EBV) has been recently found to generate novel circular RNAs (circRNAs) through backsplicing. However, comprehensive catalogs of EBV circRNAs in other cell lines and their functional characterization are still lacking. In this study, we have identified a list of putative EBV circRNAs in GM12878, an EBV-transformed lymphoblastoid cell line, with a significant majority encoded from the EBV latent genes. A novel EBV circRNA derived from the exon 5 of LMP-2 gene which exhibited highest prevalence, was further validated using RNase R assay and Sanger sequencing. This circRNA, which we term circLMP-2_e5, can be universally detected in a panel of EBV-positive cell lines modelling different latency programs. It ranges from lower expression in nasopharyngeal carcinoma (NPC) cells to higher expression in B cells, and is localized to both the cytoplasm and the nucleus. We provide evidence that circLMP-2_e5 is expressed concomitantly with its cognate linear LMP-2 RNA upon EBV lytic reactivation, and may be produced as a result of exon skipping, with its circularization possibly occurring without the involvement of cis elements in the short flanking introns. Furthermore, we show that circLMP-2_e5 is not involved in regulating cell proliferation, host innate immune response, its linear parental transcripts, or EBV lytic reactivation. Taken together, our study expands the current repertoire of putative EBV circRNAs, broadens our understanding of the biology of EBV circRNAs, and lays the foundation for further investigation of their function in the EBV life cycle and disease development.

Item Type: Article
Funders: Fundamental Research Grant Scheme[FRGS/1/2017/SKK08/UM/02/11], University of Malaya High Impact Research Grant[UM.C/625/1/HIR/MOE/CHAN/02/07], Ministry of Health Malaysia[NMRR-18-623-41161], Wellcome Trust European Commission[217389/Z/19/Z]
Uncontrolled Keywords: Lytic replication;EBV;Interference;Infection;Immunity
Subjects: R Medicine
R Medicine > RK Dentistry
Divisions: Faculty of Dentistry
Depositing User: Ms Zaharah Ramly
Date Deposited: 30 May 2022 02:25
Last Modified: 30 May 2022 02:25

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