The viral and cellular microRNA targetome in lymphoblastoid cell lines.

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus linked to a number of B cell cancers and lymphoproliferative disorders. During latent infection, EBV expresses 25 viral pre-microRNAs (miRNAs) and induces the expression of specific host miRNAs, such as miR-155 and miR-21, which potentially...

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Autores principales:	Rebecca L Skalsky, David L Corcoran, Eva Gottwein, Christopher L Frank, Dong Kang, Markus Hafner, Jeffrey D Nusbaum, Regina Feederle, Henri-Jacques Delecluse, Micah A Luftig, Thomas Tuschl, Uwe Ohler, Bryan R Cullen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a136357bf79149a6af9fde708fd1cf25
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spelling	oai:doaj.org-article:a136357bf79149a6af9fde708fd1cf252021-11-18T06:04:50ZThe viral and cellular microRNA targetome in lymphoblastoid cell lines.1553-73661553-737410.1371/journal.ppat.1002484https://doaj.org/article/a136357bf79149a6af9fde708fd1cf252012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22291592/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus linked to a number of B cell cancers and lymphoproliferative disorders. During latent infection, EBV expresses 25 viral pre-microRNAs (miRNAs) and induces the expression of specific host miRNAs, such as miR-155 and miR-21, which potentially play a role in viral oncogenesis. To date, only a limited number of EBV miRNA targets have been identified; thus, the role of EBV miRNAs in viral pathogenesis and/or lymphomagenesis is not well defined. Here, we used photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) combined with deep sequencing and computational analysis to comprehensively examine the viral and cellular miRNA targetome in EBV strain B95-8-infected lymphoblastoid cell lines (LCLs). We identified 7,827 miRNA-interaction sites in 3,492 cellular 3'UTRs. 531 of these sites contained seed matches to viral miRNAs. 24 PAR-CLIP-identified miRNA:3'UTR interactions were confirmed by reporter assays. Our results reveal that EBV miRNAs predominantly target cellular transcripts during latent infection, thereby manipulating the host environment. Furthermore, targets of EBV miRNAs are involved in multiple cellular processes that are directly relevant to viral infection, including innate immunity, cell survival, and cell proliferation. Finally, we present evidence that myc-regulated host miRNAs from the miR-17/92 cluster can regulate latent viral gene expression. This comprehensive survey of the miRNA targetome in EBV-infected B cells represents a key step towards defining the functions of EBV-encoded miRNAs, and potentially, identifying novel therapeutic targets for EBV-associated malignancies.Rebecca L SkalskyDavid L CorcoranEva GottweinChristopher L FrankDong KangMarkus HafnerJeffrey D NusbaumRegina FeederleHenri-Jacques DelecluseMicah A LuftigThomas TuschlUwe OhlerBryan R CullenPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 1, p e1002484 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Rebecca L Skalsky David L Corcoran Eva Gottwein Christopher L Frank Dong Kang Markus Hafner Jeffrey D Nusbaum Regina Feederle Henri-Jacques Delecluse Micah A Luftig Thomas Tuschl Uwe Ohler Bryan R Cullen The viral and cellular microRNA targetome in lymphoblastoid cell lines.
description	Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus linked to a number of B cell cancers and lymphoproliferative disorders. During latent infection, EBV expresses 25 viral pre-microRNAs (miRNAs) and induces the expression of specific host miRNAs, such as miR-155 and miR-21, which potentially play a role in viral oncogenesis. To date, only a limited number of EBV miRNA targets have been identified; thus, the role of EBV miRNAs in viral pathogenesis and/or lymphomagenesis is not well defined. Here, we used photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) combined with deep sequencing and computational analysis to comprehensively examine the viral and cellular miRNA targetome in EBV strain B95-8-infected lymphoblastoid cell lines (LCLs). We identified 7,827 miRNA-interaction sites in 3,492 cellular 3'UTRs. 531 of these sites contained seed matches to viral miRNAs. 24 PAR-CLIP-identified miRNA:3'UTR interactions were confirmed by reporter assays. Our results reveal that EBV miRNAs predominantly target cellular transcripts during latent infection, thereby manipulating the host environment. Furthermore, targets of EBV miRNAs are involved in multiple cellular processes that are directly relevant to viral infection, including innate immunity, cell survival, and cell proliferation. Finally, we present evidence that myc-regulated host miRNAs from the miR-17/92 cluster can regulate latent viral gene expression. This comprehensive survey of the miRNA targetome in EBV-infected B cells represents a key step towards defining the functions of EBV-encoded miRNAs, and potentially, identifying novel therapeutic targets for EBV-associated malignancies.
format	article
author	Rebecca L Skalsky David L Corcoran Eva Gottwein Christopher L Frank Dong Kang Markus Hafner Jeffrey D Nusbaum Regina Feederle Henri-Jacques Delecluse Micah A Luftig Thomas Tuschl Uwe Ohler Bryan R Cullen
author_facet	Rebecca L Skalsky David L Corcoran Eva Gottwein Christopher L Frank Dong Kang Markus Hafner Jeffrey D Nusbaum Regina Feederle Henri-Jacques Delecluse Micah A Luftig Thomas Tuschl Uwe Ohler Bryan R Cullen
author_sort	Rebecca L Skalsky
title	The viral and cellular microRNA targetome in lymphoblastoid cell lines.
title_short	The viral and cellular microRNA targetome in lymphoblastoid cell lines.
title_full	The viral and cellular microRNA targetome in lymphoblastoid cell lines.
title_fullStr	The viral and cellular microRNA targetome in lymphoblastoid cell lines.
title_full_unstemmed	The viral and cellular microRNA targetome in lymphoblastoid cell lines.
title_sort	viral and cellular microrna targetome in lymphoblastoid cell lines.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/a136357bf79149a6af9fde708fd1cf25
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The viral and cellular microRNA targetome in lymphoblastoid cell lines.

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