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Cell Type Diversity in Hepatitis B Virus RNA Splicing and Its Regulation

Although RNA splicing of hepatitis B virus (HBV) is a commonly observed in livers of hepatitis B patients as well as in the cultured cells replicating the viral genome, its biological significance in the HBV life cycle and the detailed regulatory mechanisms are still largely unclear. In this study,...

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Autores principales: Ito, Noriomi, Nakashima, Kenji, Sun, Suofeng, Ito, Masahiko, Suzuki, Tetsuro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375855/
https://www.ncbi.nlm.nih.gov/pubmed/30800119
http://dx.doi.org/10.3389/fmicb.2019.00207
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author Ito, Noriomi
Nakashima, Kenji
Sun, Suofeng
Ito, Masahiko
Suzuki, Tetsuro
author_facet Ito, Noriomi
Nakashima, Kenji
Sun, Suofeng
Ito, Masahiko
Suzuki, Tetsuro
author_sort Ito, Noriomi
collection PubMed
description Although RNA splicing of hepatitis B virus (HBV) is a commonly observed in livers of hepatitis B patients as well as in the cultured cells replicating the viral genome, its biological significance in the HBV life cycle and the detailed regulatory mechanisms are still largely unclear. In this study, we found cell-type dependency of HBV splicing of the 3.5 kb pregenomic RNA, which is efficiently spliced in human hepatoma cells but not in cells derived from human hepatic stellate, mouse hepatoma and human non-hepatic cells. It may be likely that RNA splicing is one of the determinants of host range restriction of HBV. Given the finding indicating the difference in cell-type dependency of the splicing efficiency between HBV and simian virus 40, we carried out intron-swapping experiments. The results suggest the presence of putative exonic splicing enhancer that possibly works in the cell-type dependent fashion. Together with further mutational analyses, a novel 50-nt intronic splicing silencer, whose secondary structure is well conserved among the HBV strains, was identified. It appears that this intronic silencer functions effectively independent of cell backgrounds.
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spelling pubmed-63758552019-02-22 Cell Type Diversity in Hepatitis B Virus RNA Splicing and Its Regulation Ito, Noriomi Nakashima, Kenji Sun, Suofeng Ito, Masahiko Suzuki, Tetsuro Front Microbiol Microbiology Although RNA splicing of hepatitis B virus (HBV) is a commonly observed in livers of hepatitis B patients as well as in the cultured cells replicating the viral genome, its biological significance in the HBV life cycle and the detailed regulatory mechanisms are still largely unclear. In this study, we found cell-type dependency of HBV splicing of the 3.5 kb pregenomic RNA, which is efficiently spliced in human hepatoma cells but not in cells derived from human hepatic stellate, mouse hepatoma and human non-hepatic cells. It may be likely that RNA splicing is one of the determinants of host range restriction of HBV. Given the finding indicating the difference in cell-type dependency of the splicing efficiency between HBV and simian virus 40, we carried out intron-swapping experiments. The results suggest the presence of putative exonic splicing enhancer that possibly works in the cell-type dependent fashion. Together with further mutational analyses, a novel 50-nt intronic splicing silencer, whose secondary structure is well conserved among the HBV strains, was identified. It appears that this intronic silencer functions effectively independent of cell backgrounds. Frontiers Media S.A. 2019-02-08 /pmc/articles/PMC6375855/ /pubmed/30800119 http://dx.doi.org/10.3389/fmicb.2019.00207 Text en Copyright © 2019 Ito, Nakashima, Sun, Ito and Suzuki. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Ito, Noriomi
Nakashima, Kenji
Sun, Suofeng
Ito, Masahiko
Suzuki, Tetsuro
Cell Type Diversity in Hepatitis B Virus RNA Splicing and Its Regulation
title Cell Type Diversity in Hepatitis B Virus RNA Splicing and Its Regulation
title_full Cell Type Diversity in Hepatitis B Virus RNA Splicing and Its Regulation
title_fullStr Cell Type Diversity in Hepatitis B Virus RNA Splicing and Its Regulation
title_full_unstemmed Cell Type Diversity in Hepatitis B Virus RNA Splicing and Its Regulation
title_short Cell Type Diversity in Hepatitis B Virus RNA Splicing and Its Regulation
title_sort cell type diversity in hepatitis b virus rna splicing and its regulation
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375855/
https://www.ncbi.nlm.nih.gov/pubmed/30800119
http://dx.doi.org/10.3389/fmicb.2019.00207
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