Phosphorylation of serine 177 of the small hepatitis delta antigen regulates viral antigenomic RNA replication by interacting with the processive RNA polymerase II.

Journal of Virology
Shiao-Ya Hong, Pei-Jer Chen

Abstract

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 (Ser(177)) 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 Ser(177)-phosphorylated counterpart (pSer(177)-SHDAg) exhibited preferential binding to hyperphosphorylated RNAP II (RNAP IIO). In addition, RNAP IIO associated with pSer(177)-SHDAg was hyperphosphorylated at both the Ser(2) and Ser(5) 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-beta-D-ribofuranosyl-benzimidazole (DRB) not only blocked the interaction between pSer(177)-SHDAg and RNAP IIO but also inhibited HDV antigenomic RNA replication. Our r...Continue Reading

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Citations

Aug 22, 2015·International Journal of Molecular Sciences·Zhimin Guo, Thomas King
Jan 11, 2014·World Journal of Hepatology·Zaigham Abbas, Rafia Afzal
Oct 31, 2014·World Journal of Gastroenterology : WJG·Chi-Ruei Huang, Szecheng John Lo
Jun 20, 2020·World Journal of Gastroenterology : WJG·Stephanie JungUlrike Protzer
Sep 15, 2017·Virology Journal·Luan Felipo Botelho-SouzaDeusilene Souza Vieira
Sep 19, 2019·World Journal of Gastroenterology : WJG·Christy GilmanChristopher Koh
Jan 23, 2020·Nature Communications·Natali Abeywickrama-SamarakoonPaul Dény
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May 4, 2020·Antiviral Research·Julie Lucifora, Marion Delphin
Sep 7, 2021·Expert Opinion on Investigational Drugs·Bilal Asif, Christopher Koh
Jun 14, 2019·Journal of Advanced Research·Nathalie MenthaDulce Alfaiate

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