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Article: Comparative study of regulation of RTA-responsive genes in Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8

TitleComparative study of regulation of RTA-responsive genes in Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8
Authors
Issue Date2003
Citation
Journal of Virology, 2003, v. 77, n. 17, p. 9451-9462 How to Cite?
AbstractReplication and transcription activator (RTA) (also referred to as ORF50), an immediate-early gene product of Kaposi's sarcoma-associated herpesvirus (KSHV)/(human herpesvirus 8), plays a critical role in balancing the viral life cycle between latency and lytic replication. RTA has been shown to act as a strong transcription activator for several downstream genes of KSHV. Direct binding of RTA to DNA is thought to be one of the important mechanisms for transactivation of target genes, while indirect mechanisms are also implicated in RTA transactivation of certain selected genes. This study demonstrated direct binding of the DNA-binding domain of RTA (Rdbd) to a Kaposin (Kpsn) promoter sequence, which is highly homologous to the RTA-responsive element (RRE) of the PAN promoter. We undertook a comparative study of the RREs of PAN RNA, ORF57, vIL-6, and Kpsn to understand how RTA regulates gene expression during lytic replication. Comparing RNA abundance and transcription initiation rates of these RTA target genes in virus-infected cells suggested that the transcription initiation rate of the promoters is a major determinant of viral gene expression, rather than stability of the transcripts. RTA-mediated transactivation of reporters containing each RRE showed that their promoter strengths in a transient-transfection system were comparable to their transcription rates during reactivation. Moreover, our electrophoretic mobility shift assays of each RRE demonstrated that the highly purified Rdbd protein directly bound to the RREs. Based on these results, we conclude that direct binding of RTA to these target sequences contributes to their gene expression to various extents during the lytic life cycle of KSHV.
Persistent Identifierhttp://hdl.handle.net/10722/285577
ISSN
2023 Impact Factor: 4.0
2023 SCImago Journal Rankings: 1.378
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSong, Moon Jung-
dc.contributor.authorDeng, Hongyu-
dc.contributor.authorSun, Ren-
dc.date.accessioned2020-08-18T04:56:06Z-
dc.date.available2020-08-18T04:56:06Z-
dc.date.issued2003-
dc.identifier.citationJournal of Virology, 2003, v. 77, n. 17, p. 9451-9462-
dc.identifier.issn0022-538X-
dc.identifier.urihttp://hdl.handle.net/10722/285577-
dc.description.abstractReplication and transcription activator (RTA) (also referred to as ORF50), an immediate-early gene product of Kaposi's sarcoma-associated herpesvirus (KSHV)/(human herpesvirus 8), plays a critical role in balancing the viral life cycle between latency and lytic replication. RTA has been shown to act as a strong transcription activator for several downstream genes of KSHV. Direct binding of RTA to DNA is thought to be one of the important mechanisms for transactivation of target genes, while indirect mechanisms are also implicated in RTA transactivation of certain selected genes. This study demonstrated direct binding of the DNA-binding domain of RTA (Rdbd) to a Kaposin (Kpsn) promoter sequence, which is highly homologous to the RTA-responsive element (RRE) of the PAN promoter. We undertook a comparative study of the RREs of PAN RNA, ORF57, vIL-6, and Kpsn to understand how RTA regulates gene expression during lytic replication. Comparing RNA abundance and transcription initiation rates of these RTA target genes in virus-infected cells suggested that the transcription initiation rate of the promoters is a major determinant of viral gene expression, rather than stability of the transcripts. RTA-mediated transactivation of reporters containing each RRE showed that their promoter strengths in a transient-transfection system were comparable to their transcription rates during reactivation. Moreover, our electrophoretic mobility shift assays of each RRE demonstrated that the highly purified Rdbd protein directly bound to the RREs. Based on these results, we conclude that direct binding of RTA to these target sequences contributes to their gene expression to various extents during the lytic life cycle of KSHV.-
dc.languageeng-
dc.relation.ispartofJournal of Virology-
dc.titleComparative study of regulation of RTA-responsive genes in Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1128/JVI.77.17.9451-9462.2003-
dc.identifier.pmid12915560-
dc.identifier.pmcidPMC187374-
dc.identifier.scopuseid_2-s2.0-0041387440-
dc.identifier.volume77-
dc.identifier.issue17-
dc.identifier.spage9451-
dc.identifier.epage9462-
dc.identifier.isiWOS:000184776800034-
dc.identifier.issnl0022-538X-

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