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

Abstract 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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ke-En Tan, Wei Lun Ng, Georgi K. Marinov, Ken Hung-On Yu, Lu Ping Tan, Ee Shan Liau, Sook Yan Goh, Kok Siong Yeo, Kevin Y. Yip, Kwok-Wai Lo, Alan Soo-Beng Khoo, Lee-Fah Yap, Chee-Kwee Ea, Yat-Yuen Lim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6f280b89ec074aafa9b102c63d7b3441
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6f280b89ec074aafa9b102c63d7b3441
record_format	dspace
spelling	oai:doaj.org-article:6f280b89ec074aafa9b102c63d7b34412021-12-02T16:14:16ZIdentification and characterization of a novel Epstein-Barr Virus-encoded circular RNA from LMP-2 Gene10.1038/s41598-021-93781-w2045-2322https://doaj.org/article/6f280b89ec074aafa9b102c63d7b34412021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93781-whttps://doaj.org/toc/2045-2322Abstract 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.Ke-En TanWei Lun NgGeorgi K. MarinovKen Hung-On YuLu Ping TanEe Shan LiauSook Yan GohKok Siong YeoKevin Y. YipKwok-Wai LoAlan Soo-Beng KhooLee-Fah YapChee-Kwee EaYat-Yuen LimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ke-En Tan Wei Lun Ng Georgi K. Marinov Ken Hung-On Yu Lu Ping Tan Ee Shan Liau Sook Yan Goh Kok Siong Yeo Kevin Y. Yip Kwok-Wai Lo Alan Soo-Beng Khoo Lee-Fah Yap Chee-Kwee Ea Yat-Yuen Lim Identification and characterization of a novel Epstein-Barr Virus-encoded circular RNA from LMP-2 Gene
description	Abstract 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.
format	article
author	Ke-En Tan Wei Lun Ng Georgi K. Marinov Ken Hung-On Yu Lu Ping Tan Ee Shan Liau Sook Yan Goh Kok Siong Yeo Kevin Y. Yip Kwok-Wai Lo Alan Soo-Beng Khoo Lee-Fah Yap Chee-Kwee Ea Yat-Yuen Lim
author_facet	Ke-En Tan Wei Lun Ng Georgi K. Marinov Ken Hung-On Yu Lu Ping Tan Ee Shan Liau Sook Yan Goh Kok Siong Yeo Kevin Y. Yip Kwok-Wai Lo Alan Soo-Beng Khoo Lee-Fah Yap Chee-Kwee Ea Yat-Yuen Lim
author_sort	Ke-En Tan
title	Identification and characterization of a novel Epstein-Barr Virus-encoded circular RNA from LMP-2 Gene
title_short	Identification and characterization of a novel Epstein-Barr Virus-encoded circular RNA from LMP-2 Gene
title_full	Identification and characterization of a novel Epstein-Barr Virus-encoded circular RNA from LMP-2 Gene
title_fullStr	Identification and characterization of a novel Epstein-Barr Virus-encoded circular RNA from LMP-2 Gene
title_full_unstemmed	Identification and characterization of a novel Epstein-Barr Virus-encoded circular RNA from LMP-2 Gene
title_sort	identification and characterization of a novel epstein-barr virus-encoded circular rna from lmp-2 gene
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6f280b89ec074aafa9b102c63d7b3441
work_keys_str_mv	AT keentan identificationandcharacterizationofanovelepsteinbarrvirusencodedcircularrnafromlmp2gene AT weilunng identificationandcharacterizationofanovelepsteinbarrvirusencodedcircularrnafromlmp2gene AT georgikmarinov identificationandcharacterizationofanovelepsteinbarrvirusencodedcircularrnafromlmp2gene AT kenhungonyu identificationandcharacterizationofanovelepsteinbarrvirusencodedcircularrnafromlmp2gene AT lupingtan identificationandcharacterizationofanovelepsteinbarrvirusencodedcircularrnafromlmp2gene AT eeshanliau identificationandcharacterizationofanovelepsteinbarrvirusencodedcircularrnafromlmp2gene AT sookyangoh identificationandcharacterizationofanovelepsteinbarrvirusencodedcircularrnafromlmp2gene AT koksiongyeo identificationandcharacterizationofanovelepsteinbarrvirusencodedcircularrnafromlmp2gene AT kevinyyip identificationandcharacterizationofanovelepsteinbarrvirusencodedcircularrnafromlmp2gene AT kwokwailo identificationandcharacterizationofanovelepsteinbarrvirusencodedcircularrnafromlmp2gene AT alansoobengkhoo identificationandcharacterizationofanovelepsteinbarrvirusencodedcircularrnafromlmp2gene AT leefahyap identificationandcharacterizationofanovelepsteinbarrvirusencodedcircularrnafromlmp2gene AT cheekweeea identificationandcharacterizationofanovelepsteinbarrvirusencodedcircularrnafromlmp2gene AT yatyuenlim identificationandcharacterizationofanovelepsteinbarrvirusencodedcircularrnafromlmp2gene
_version_	1718384355815981056

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

Ejemplares similares