title: TGF-β suppression of HBV RNA through AID-dependent recruitment of an RNA exosome complex.
abstract: Transforming growth factor (TGF)-β inhibits hepatitis B virus (HBV) replication although the intracellular effectors involved are not determined. Here, we report that reduction of HBV transcripts by TGF-β is dependent on AID expression, which significantly decreases both HBV transcripts and viral DNA, resulting in inhibition of viral replication. Immunoprecipitation reveals that AID physically associates with viral P protein that binds to specific virus RNA sequence called epsilon. AID also binds to an RNA degradation complex (RNA exosome proteins), indicating that AID, RNA exosome, and P protein form an RNP complex. Suppression of HBV transcripts by TGF-β was abrogated by depletion of either AID or RNA exosome components, suggesting that AID and the RNA exosome involve in TGF-β mediated suppression of HBV RNA. Moreover, AID-mediated HBV reduction does not occur when P protein is disrupted or when viral transcription is inhibited. These results suggest that induced expression of AID by TGF-β causes recruitment of the RNA exosome to viral RNP complex and the RNA exosome degrades HBV RNA in a transcription-coupled manner.
authors.affiliation: Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan; Department of Microbiology and Immunology, Columbia University, New York, New York, United States of America.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Liang
authors.affiliation: Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Guangyan
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Kitamura
authors.affiliation: Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan; Division of Medical Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Sajeda
authors.initials: S
authors.lastname: Chowdhury
authors.affiliation: Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Ahasan Md
authors.initials: AM
authors.lastname: Monjurul
authors.affiliation: Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Kousho
authors.initials: K
authors.lastname: Wakae
authors.affiliation: Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Koura
authors.affiliation: Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Shimadu
authors.affiliation: Evolutionary Medicine, Shiga Medical Center Research Institute, Moriyama, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kinoshita
authors.affiliation: Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Muramatsu
mesh_terms: D000071478:APOBEC Deaminases; D015153:Blotting, Western; D002460:Cell Line; D003564:Cytidine Deaminase / Q000378:metabolism*; D043525:Cytosine Deaminase / Q000378:metabolism; D063326:Exosome Multienzyme Ribonuclease Complex / Q000378:metabolism*; D006509:Hepatitis B / Q000235:genetics; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D012367:RNA, Viral; D016212:Transforming Growth Factor beta; D063326:Exosome Multienzyme Ribonuclease Complex; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase
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