Ago HITS-CLIP expands understanding of Kaposi's sarcoma-associated herpesvirus miRNA function in primary effusion lymphomas.

KSHV is the etiological agent of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and a subset of multicentricCastleman's disease (MCD). The fact that KSHV-encoded miRNAs are readily detectable in all KSHV-associated tumors suggests a potential role in viral pathogenesis and tumorig...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Irina Haecker, Lauren A Gay, Yajie Yang, Jianhong Hu, Alison M Morse, Lauren M McIntyre, Rolf Renne
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/7d076f14e76a43a09b24dc709d769696
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7d076f14e76a43a09b24dc709d769696
record_format	dspace
spelling	oai:doaj.org-article:7d076f14e76a43a09b24dc709d7696962021-11-18T06:04:02ZAgo HITS-CLIP expands understanding of Kaposi's sarcoma-associated herpesvirus miRNA function in primary effusion lymphomas.1553-73661553-737410.1371/journal.ppat.1002884https://doaj.org/article/7d076f14e76a43a09b24dc709d7696962012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22927820/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374KSHV is the etiological agent of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and a subset of multicentricCastleman's disease (MCD). The fact that KSHV-encoded miRNAs are readily detectable in all KSHV-associated tumors suggests a potential role in viral pathogenesis and tumorigenesis. MiRNA-mediated regulation of gene expression is a complex network with each miRNA having many potential targets, and to date only few KSHV miRNA targets have been experimentally determined. A detailed understanding of KSHV miRNA functions requires high-through putribonomics to globally analyze putative miRNA targets in a cell type-specific manner. We performed Ago HITS-CLIP to identify viral and cellular miRNAs and their cognate targets in two latently KSHV-infected PEL cell lines. Ago HITS-CLIP recovered 1170 and 950 cellular KSHV miRNA targets from BCBL-1 and BC-3, respectively. Importantly, enriched clusters contained KSHV miRNA seed matches in the 3'UTRs of numerous well characterized targets, among them THBS1, BACH1, and C/EBPβ. KSHV miRNA targets were strongly enriched for genes involved in multiple pathways central for KSHV biology, such as apoptosis, cell cycle regulation, lymphocyte proliferation, and immune evasion, thus further supporting a role in KSHV pathogenesis and potentially tumorigenesis. A limited number of viral transcripts were also enriched by HITS-CLIP including vIL-6 expressed only in a subset of PEL cells during latency. Interestingly, Ago HITS-CLIP revealed extremely high levels of Ago-associated KSHV miRNAs especially in BC-3 cells where more than 70% of all miRNAs are of viral origin. This suggests that in addition to seed match-specific targeting of cellular genes, KSHV miRNAs may also function by hijacking RISCs, thereby contributing to a global de-repression of cellular gene expression due to the loss of regulation by human miRNAs. In summary, we provide an extensive list of cellular and viral miRNA targets representing an important resource to decipher KSHV miRNA function.Irina HaeckerLauren A GayYajie YangJianhong HuAlison M MorseLauren M McIntyreRolf RennePublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 8, p e1002884 (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 Irina Haecker Lauren A Gay Yajie Yang Jianhong Hu Alison M Morse Lauren M McIntyre Rolf Renne Ago HITS-CLIP expands understanding of Kaposi's sarcoma-associated herpesvirus miRNA function in primary effusion lymphomas.
description	KSHV is the etiological agent of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and a subset of multicentricCastleman's disease (MCD). The fact that KSHV-encoded miRNAs are readily detectable in all KSHV-associated tumors suggests a potential role in viral pathogenesis and tumorigenesis. MiRNA-mediated regulation of gene expression is a complex network with each miRNA having many potential targets, and to date only few KSHV miRNA targets have been experimentally determined. A detailed understanding of KSHV miRNA functions requires high-through putribonomics to globally analyze putative miRNA targets in a cell type-specific manner. We performed Ago HITS-CLIP to identify viral and cellular miRNAs and their cognate targets in two latently KSHV-infected PEL cell lines. Ago HITS-CLIP recovered 1170 and 950 cellular KSHV miRNA targets from BCBL-1 and BC-3, respectively. Importantly, enriched clusters contained KSHV miRNA seed matches in the 3'UTRs of numerous well characterized targets, among them THBS1, BACH1, and C/EBPβ. KSHV miRNA targets were strongly enriched for genes involved in multiple pathways central for KSHV biology, such as apoptosis, cell cycle regulation, lymphocyte proliferation, and immune evasion, thus further supporting a role in KSHV pathogenesis and potentially tumorigenesis. A limited number of viral transcripts were also enriched by HITS-CLIP including vIL-6 expressed only in a subset of PEL cells during latency. Interestingly, Ago HITS-CLIP revealed extremely high levels of Ago-associated KSHV miRNAs especially in BC-3 cells where more than 70% of all miRNAs are of viral origin. This suggests that in addition to seed match-specific targeting of cellular genes, KSHV miRNAs may also function by hijacking RISCs, thereby contributing to a global de-repression of cellular gene expression due to the loss of regulation by human miRNAs. In summary, we provide an extensive list of cellular and viral miRNA targets representing an important resource to decipher KSHV miRNA function.
format	article
author	Irina Haecker Lauren A Gay Yajie Yang Jianhong Hu Alison M Morse Lauren M McIntyre Rolf Renne
author_facet	Irina Haecker Lauren A Gay Yajie Yang Jianhong Hu Alison M Morse Lauren M McIntyre Rolf Renne
author_sort	Irina Haecker
title	Ago HITS-CLIP expands understanding of Kaposi's sarcoma-associated herpesvirus miRNA function in primary effusion lymphomas.
title_short	Ago HITS-CLIP expands understanding of Kaposi's sarcoma-associated herpesvirus miRNA function in primary effusion lymphomas.
title_full	Ago HITS-CLIP expands understanding of Kaposi's sarcoma-associated herpesvirus miRNA function in primary effusion lymphomas.
title_fullStr	Ago HITS-CLIP expands understanding of Kaposi's sarcoma-associated herpesvirus miRNA function in primary effusion lymphomas.
title_full_unstemmed	Ago HITS-CLIP expands understanding of Kaposi's sarcoma-associated herpesvirus miRNA function in primary effusion lymphomas.
title_sort	ago hits-clip expands understanding of kaposi's sarcoma-associated herpesvirus mirna function in primary effusion lymphomas.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/7d076f14e76a43a09b24dc709d769696
work_keys_str_mv	AT irinahaecker agohitsclipexpandsunderstandingofkaposissarcomaassociatedherpesvirusmirnafunctioninprimaryeffusionlymphomas AT laurenagay agohitsclipexpandsunderstandingofkaposissarcomaassociatedherpesvirusmirnafunctioninprimaryeffusionlymphomas AT yajieyang agohitsclipexpandsunderstandingofkaposissarcomaassociatedherpesvirusmirnafunctioninprimaryeffusionlymphomas AT jianhonghu agohitsclipexpandsunderstandingofkaposissarcomaassociatedherpesvirusmirnafunctioninprimaryeffusionlymphomas AT alisonmmorse agohitsclipexpandsunderstandingofkaposissarcomaassociatedherpesvirusmirnafunctioninprimaryeffusionlymphomas AT laurenmmcintyre agohitsclipexpandsunderstandingofkaposissarcomaassociatedherpesvirusmirnafunctioninprimaryeffusionlymphomas AT rolfrenne agohitsclipexpandsunderstandingofkaposissarcomaassociatedherpesvirusmirnafunctioninprimaryeffusionlymphomas
_version_	1718424612519280640

Ago HITS-CLIP expands understanding of Kaposi's sarcoma-associated herpesvirus miRNA function in primary effusion lymphomas.

Ejemplares similares