https://scholars.lib.ntu.edu.tw/handle/123456789/568567
標題: | Phosphorylation of serine 177 of the small hepatitis delta antigen regulates viral antigenomic RNA replication by interacting with the processive rna polymerase II | 作者: | Hong S.-Y. PEI-JER CHEN |
公開日期: | 2010 | 出版社: | American Society for Microbiology | 卷: | 84 | 期: | 3 | 起(迄)頁: | 1430-1438 | 來源出版物: | Journal of Virology | 摘要: | Recent studies revealed that posttranslational modifications (e.g., phosphorylation and methylation) of the small hepatitis delta antigen (SHDAg) are required for hepatitis delta virus (HDV) replication from antigenomic to genomic RNA. The phosphorylation of SHDAg at serine 177 (Ser177) is involved in this step, and this residue is crucial for interaction with RNA polymerase II (RNAP II), the enzyme assumed to be responsible for antigenomic RNA replication. This study demonstrated that SHDAg dephosphorylated at Ser 177 interacted preferentially with hypophosphorylated RNAP II (RNAP IIA), which generally binds at the transcription initiation sites. In contrast, the Ser177-phosphorylated counterpart (pSer177-SHDAg) exhibited preferential binding to hyperphosphorylated RNAP II (RNAP IIO). In addition, RNAP IIO associated with pSer177-SHDAg was hyperphosphorylated at both the Ser2 and Ser5 residues of its carboxyl-terminal domain (CTD), which is a hallmark of the transcription elongation isoform. Moreover, the RNAP II CTD kinase inhibitor 5,6-dichloro-1-β-D-ribofuranosyl-benzimidazole (DRB) not only blocked the interaction between pSer177-SHDAg and RNAP IIO but also inhibited HDV antigenomic replication. Our results suggest that the phosphorylation of SHDAg at Ser177 shifted its affinity toward the RNA RNAP IIO isoform and thus is a switch for HDV antigenomic RNA replication from the initiation to the elongation stage. Copyright ? 2010, American Society for Microbiology. All Rights Reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84984539825&doi=10.1128%2fJVI.02083-09&partnerID=40&md5=cbdb86e8084889204bfa5e0676594743 https://scholars.lib.ntu.edu.tw/handle/123456789/568567 |
ISSN: | 0022-538X | DOI: | 10.1128/JVI.02083-09 | SDG/關鍵字: | 5,6 dichloro 1 beta dextro ribofuranosyl benzimidazole; antinuclear antibody; enzyme inhibitor; hepatitis delta antigen; RNA polymerase II; serine; transcription elongation factor; unclassified drug; article; cell nucleus inclusion body; controlled study; gene control; human; human cell; priority journal; protein binding; protein dephosphorylation; protein interaction; protein localization; protein phosphorylation; RNA replication; virus replication; Hepatitis delta virus |
顯示於: | 臨床醫學研究所 |
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