title: Multiple regions of Kaposi's sarcoma-associated herpesvirus ORF59 RNA are required for its expression mediated by viral ORF57 and cellular RBM15.
abstract: KSHV ORF57 (MTA) promotes RNA stability of ORF59, a viral DNA polymerase processivity factor. Here, we show that the integrity of both ORF59 RNA ends is necessary for ORF57-mediated ORF59 expression and deletion of both 5' and 3' regions, or one end region with a central region, of ORF59 RNA prevents ORF57-mediated translation of ORF59. The ORF59 sequence between nt 96633 and 96559 resembles other known MTA-responsive elements (MREs). ORF57 specifically binds to a stem-loop region from nt 96596-96572 of the MRE, which also binds cellular RBM15. Internal deletion of the MRE from ORF59 led to poor export, but accumulation of nuclear ORF59 RNA in the presence of ORF57 or RBM15. Despite of being translatable in the presence of ORF57, this deletion mutant exhibits translational defect in the presence of RBM15. Together, our results provide novel insight into the roles of ORF57 and RBM15 in ORF59 RNA accumulation and protein translation.
authors.affiliation: Tumor Virus RNA Biology Section, Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 1050 Boyles Street, Frederick, MD 21702, USA. julia.massimelli@uci.edu.
authors.forename: Maria Julia
authors.initials: MJ
authors.lastname: Massimelli
authors.affiliation: Tumor Virus RNA Biology Section, Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 1050 Boyles Street, Frederick, MD 21702, USA. majerciv@mail.nih.gov.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Majerciak
authors.affiliation: Tumor Virus RNA Biology Section, Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 1050 Boyles Street, Frederick, MD 21702, USA. jkang@jkbiopharma.com.
authors.forename: Jeong-Gu
authors.initials: JG
authors.lastname: Kang
authors.affiliation: Biostatistics & Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. liewehrd@mail.nih.gov.
authors.forename: David J
authors.initials: DJ
authors.lastname: Liewehr
authors.affiliation: Biostatistics & Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. steinbes@mail.nih.gov.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.affiliation: Tumor Virus RNA Biology Section, Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 1050 Boyles Street, Frederick, MD 21702, USA. zhengt@exchange.nih.gov.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Zheng
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D004843:Epistasis, Genetic; D015967:Gene Expression Regulation, Viral; D006566:Herpesviridae Infections / Q000378:metabolism / Q000821:virology; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D034443:RNA Transport; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D020218:Response Elements; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C000598480:ORF57 protein, human herpesvirus 8; C110348:ORF59 protein, Human herpesvirus 8; C431574:RBM15 protein, human; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins