title: Kaposi's sarcoma-associated herpesvirus ORF57 protein enhances mRNA accumulation independently of effects on nuclear RNA export.
abstract: The ORF57 protein expressed by Kaposi's sarcoma-associated herpesvirus (KSHV) during lytic replication is essential for KSHV virion production. ORF57 enhances gene expression by increasing accumulation of target gene mRNAs. ORF57 interacts with the cellular export factor REF and with RNA, suggesting that it may provide target mRNAs with access to REF, which mediates nuclear RNA export by binding to TAP/NXF1. A mutational analysis of ORF57 was performed to study the role of REF binding, RNA interaction, and multimerization in ORF57 function. ORF57 was shown to directly bind RNA. The ability to bind REF did not correlate with ORF57 function in enhancing mRNA accumulation. ORF57 enhanced the nuclear levels of mRNA and PAN, a nuclear KSHV RNA, and the activity of various ORF57 mutants on the levels of mRNA paralleled their ability to enhance nuclear PAN accumulation, suggesting that ORF57 may also act on messenger RNAs by export-independent effects on RNA stability. Finally, an ORF57 mutant lacking a region homologous to a nucleolar localization signal in herpesvirus saimiri was constructed. This mutant retained function, demonstrating that, unlike the ORF57 homolog in herpesvirus saimiri, nucleolar trafficking is not required for ORF57 function in enhancing mRNA accumulation.
authors.affiliation: UF Shands Cancer Center, University of Florida, 1376 Mowry Road, Gainesville, FL 32610-3633, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Nekorchuk
authors.forename: Zhao
authors.initials: Z
authors.lastname: Han
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Hsieh
authors.forename: Sankar
authors.initials: S
authors.lastname: Swaminathan
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D006367:HeLa Cells; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism; D016366:Open Reading Frames / Q000502:physiology*; D011485:Protein Binding / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*
chemical_list: C492666:NFX1 protein, human; D019913:Nuclear Localization Signals; C415247:ORF57 protein, Herpesvirus saimiri; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins