A human cytomegalovirus-encoded microRNA regulates expression of multiple viral genes involved in replication.

Although multiple studies have documented the expression of over 70 novel virus-encoded microRNAs (miRNAs), the targets and functions of most of these regulatory RNA species are unknown. In this study a comparative bioinformatics approach was employed to identify potential human cytomegalovirus (HCM...

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Autores principales:	Finn Grey, Heather Meyers, Elizabeth A White, Deborah H Spector, Jay Nelson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2007
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b74a1333d6b3415faa2180ff4cb04888
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spelling	oai:doaj.org-article:b74a1333d6b3415faa2180ff4cb048882021-11-25T05:46:20ZA human cytomegalovirus-encoded microRNA regulates expression of multiple viral genes involved in replication.1553-73661553-737410.1371/journal.ppat.0030163https://doaj.org/article/b74a1333d6b3415faa2180ff4cb048882007-11-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.0030163https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Although multiple studies have documented the expression of over 70 novel virus-encoded microRNAs (miRNAs), the targets and functions of most of these regulatory RNA species are unknown. In this study a comparative bioinformatics approach was employed to identify potential human cytomegalovirus (HCMV) mRNA targets of the virus-encoded miRNA miR-UL112-1. Bioinformatics analysis of the known HCMV mRNA 3' untranslated regions (UTRs) revealed 14 potential viral transcripts that were predicted to contain functional target sites for miR-UL112-1. The potential target sites were screened using luciferase reporters that contain the HCMV 3'UTRs in co-transfection assays with miR-UL112-1. Three of the 14 HCMV miRNA targets were validated, including the major immediate early gene encoding IE72 (UL123, IE1), UL112/113, and UL120/121. Further analysis of IE72 regulation by miR-UL112-1 with clones encoding the complete major immediate early region revealed that the IE72 3'UTR target site is necessary and sufficient to direct miR-UL112-1-specific inhibition of expression in transfected cells. In addition, miR-UL112-1 regulation is mediated through translational inhibition rather than RNA degradation. Premature expression of miR-UL112-1 during HCMV infection resulted in a significant decrease in genomic viral DNA levels, suggesting a functional role for miR-UL112-1 in regulating the expression of genes involved in viral replication. This study demonstrates the ability of a viral miRNA to regulate multiple viral genes.Finn GreyHeather MeyersElizabeth A WhiteDeborah H SpectorJay NelsonPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 3, Iss 11, p e163 (2007)
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 Finn Grey Heather Meyers Elizabeth A White Deborah H Spector Jay Nelson A human cytomegalovirus-encoded microRNA regulates expression of multiple viral genes involved in replication.
description	Although multiple studies have documented the expression of over 70 novel virus-encoded microRNAs (miRNAs), the targets and functions of most of these regulatory RNA species are unknown. In this study a comparative bioinformatics approach was employed to identify potential human cytomegalovirus (HCMV) mRNA targets of the virus-encoded miRNA miR-UL112-1. Bioinformatics analysis of the known HCMV mRNA 3' untranslated regions (UTRs) revealed 14 potential viral transcripts that were predicted to contain functional target sites for miR-UL112-1. The potential target sites were screened using luciferase reporters that contain the HCMV 3'UTRs in co-transfection assays with miR-UL112-1. Three of the 14 HCMV miRNA targets were validated, including the major immediate early gene encoding IE72 (UL123, IE1), UL112/113, and UL120/121. Further analysis of IE72 regulation by miR-UL112-1 with clones encoding the complete major immediate early region revealed that the IE72 3'UTR target site is necessary and sufficient to direct miR-UL112-1-specific inhibition of expression in transfected cells. In addition, miR-UL112-1 regulation is mediated through translational inhibition rather than RNA degradation. Premature expression of miR-UL112-1 during HCMV infection resulted in a significant decrease in genomic viral DNA levels, suggesting a functional role for miR-UL112-1 in regulating the expression of genes involved in viral replication. This study demonstrates the ability of a viral miRNA to regulate multiple viral genes.
format	article
author	Finn Grey Heather Meyers Elizabeth A White Deborah H Spector Jay Nelson
author_facet	Finn Grey Heather Meyers Elizabeth A White Deborah H Spector Jay Nelson
author_sort	Finn Grey
title	A human cytomegalovirus-encoded microRNA regulates expression of multiple viral genes involved in replication.
title_short	A human cytomegalovirus-encoded microRNA regulates expression of multiple viral genes involved in replication.
title_full	A human cytomegalovirus-encoded microRNA regulates expression of multiple viral genes involved in replication.
title_fullStr	A human cytomegalovirus-encoded microRNA regulates expression of multiple viral genes involved in replication.
title_full_unstemmed	A human cytomegalovirus-encoded microRNA regulates expression of multiple viral genes involved in replication.
title_sort	human cytomegalovirus-encoded microrna regulates expression of multiple viral genes involved in replication.
publisher	Public Library of Science (PLoS)
publishDate	2007
url	https://doaj.org/article/b74a1333d6b3415faa2180ff4cb04888
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A human cytomegalovirus-encoded microRNA regulates expression of multiple viral genes involved in replication.

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