title: LUC7L3/CROP inhibits replication of hepatitis B virus via suppressing enhancer II/basal core promoter activity.
abstract: The core promoter of hepatitis B virus (HBV) genome is a critical region for transcriptional initiation of 3.5 kb, pregenome and precore RNAs and for the viral replication. Although a number of host-cell factors that potentially regulate the viral promoter activities have been identified, the molecular mechanisms of the viral gene expression, in particular, regulatory mechanisms of the transcriptional repression remain elusive. In this study, we identified LUC7 like 3 pre-mRNA splicing factor (LUC7L3, also known as hLuc7A or CROP) as a novel interacting partner of HBV enhancer II and basal core promoter (ENII/BCP), key elements within the core promoter, through the proteomic screening and found that LUC7L3 functions as a negative regulator of ENII/BCP. Gene silencing of LUC7L3 significantly increased expression of the viral genes and antigens as well as the activities of ENII/BCP and core promoter. In contrast, overexpression of LUC7L3 inhibited their activities and HBV replication. In addition, LUC7L3 possibly contributes to promotion of the splicing of 3.5 kb RNA, which may also be involved in negative regulation of the pregenome RNA level. This is the first to demonstrate the involvement of LUC7L3 in regulation of gene transcription and in viral replication.
authors.affiliation: Department of Virology and Parasitology, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Virology and Parasitology, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Virology and Parasitology, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan.
authors.forename: Suofeng
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Virology and Parasitology, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Chida
authors.affiliation: Department of Virology and Parasitology, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakashima
authors.affiliation: Department of Virology and Parasitology, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D006515:Hepatitis B virus / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000502:physiology*; D014158:Transcription, Genetic; D014758:Viral Core Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
chemical_list: C404083:LUC7L3 protein, human; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; C100808:pgRNA; D012313:RNA