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LINC01431 Promotes Histone H4R3 Methylation to Impede HBV Covalently Closed Circular DNA Transcription by Stabilizing PRMT1

Covalently closed circular DNA (cccDNA) is the transcriptional template of hepatitis B virus (HBV), which interacts with both host and viral proteins to form minichromosome in the nucleus and is resistant to antiviral agents. Identification of host factors involved in cccDNA transcriptional regulati...

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Autores principales: Sun, Yang, Teng, Yan, Wang, Liyuan, Zhang, Zhaoying, Chen, ChaoJia, Wang, Yingchun, Zhang, Xiaodong, Xiang, Peng, Song, Xiaojia, Lu, Jinghui, Li, Nailin, Gao, Lifen, Liang, Xiaohong, Xia, Yuchen, Wu, Zhuanchang, Ma, Chunhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165498/
https://www.ncbi.nlm.nih.gov/pubmed/35398991
http://dx.doi.org/10.1002/advs.202103135
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author Sun, Yang
Teng, Yan
Wang, Liyuan
Zhang, Zhaoying
Chen, ChaoJia
Wang, Yingchun
Zhang, Xiaodong
Xiang, Peng
Song, Xiaojia
Lu, Jinghui
Li, Nailin
Gao, Lifen
Liang, Xiaohong
Xia, Yuchen
Wu, Zhuanchang
Ma, Chunhong
author_facet Sun, Yang
Teng, Yan
Wang, Liyuan
Zhang, Zhaoying
Chen, ChaoJia
Wang, Yingchun
Zhang, Xiaodong
Xiang, Peng
Song, Xiaojia
Lu, Jinghui
Li, Nailin
Gao, Lifen
Liang, Xiaohong
Xia, Yuchen
Wu, Zhuanchang
Ma, Chunhong
author_sort Sun, Yang
collection PubMed
description Covalently closed circular DNA (cccDNA) is the transcriptional template of hepatitis B virus (HBV), which interacts with both host and viral proteins to form minichromosome in the nucleus and is resistant to antiviral agents. Identification of host factors involved in cccDNA transcriptional regulation is expected to prove a new venue for HBV therapy. Recent evidence suggests the involvement of long noncoding RNAs (lncRNAs) in mediating the interaction of host factors with various viruses, however, lncRNAs that HBV targets and represses cccDNA transcription have not been fully elucidated. Here, the authors identified LINC01431 as a novel host restriction factor for HBV transcription. Mechanically, LINC01431 competitively bound with type I protein arginine methyltransferase (PRMT1) to block the HBx‐mediated PRMT1 ubiquitination and degradation. Consequently, LINC01431 increased the occupancy of PRMT1 on cccDNA, leading to enhanced H4R3me2a modification and reduced acetylation of cccDNA‐bound histones, thereby repressing cccDNA transcription. In turn, to facilitate viral replication, HBV transcriptionally repressed LINC01431 expression by HBx‐mediated repression of transcription factor Zinc fingers and homeoboxes 2 (ZHX2). Collectively, the study demonstrates LINC01431 as a novel epigenetic regulator of cccDNA minichromosome and highlights a feedback loop of HBx‐LINC01431‐PRMT1 in HBV replication, which provides potential therapeutic targets for HBV treatment.
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spelling pubmed-91654982022-06-04 LINC01431 Promotes Histone H4R3 Methylation to Impede HBV Covalently Closed Circular DNA Transcription by Stabilizing PRMT1 Sun, Yang Teng, Yan Wang, Liyuan Zhang, Zhaoying Chen, ChaoJia Wang, Yingchun Zhang, Xiaodong Xiang, Peng Song, Xiaojia Lu, Jinghui Li, Nailin Gao, Lifen Liang, Xiaohong Xia, Yuchen Wu, Zhuanchang Ma, Chunhong Adv Sci (Weinh) Research Articles Covalently closed circular DNA (cccDNA) is the transcriptional template of hepatitis B virus (HBV), which interacts with both host and viral proteins to form minichromosome in the nucleus and is resistant to antiviral agents. Identification of host factors involved in cccDNA transcriptional regulation is expected to prove a new venue for HBV therapy. Recent evidence suggests the involvement of long noncoding RNAs (lncRNAs) in mediating the interaction of host factors with various viruses, however, lncRNAs that HBV targets and represses cccDNA transcription have not been fully elucidated. Here, the authors identified LINC01431 as a novel host restriction factor for HBV transcription. Mechanically, LINC01431 competitively bound with type I protein arginine methyltransferase (PRMT1) to block the HBx‐mediated PRMT1 ubiquitination and degradation. Consequently, LINC01431 increased the occupancy of PRMT1 on cccDNA, leading to enhanced H4R3me2a modification and reduced acetylation of cccDNA‐bound histones, thereby repressing cccDNA transcription. In turn, to facilitate viral replication, HBV transcriptionally repressed LINC01431 expression by HBx‐mediated repression of transcription factor Zinc fingers and homeoboxes 2 (ZHX2). Collectively, the study demonstrates LINC01431 as a novel epigenetic regulator of cccDNA minichromosome and highlights a feedback loop of HBx‐LINC01431‐PRMT1 in HBV replication, which provides potential therapeutic targets for HBV treatment. John Wiley and Sons Inc. 2022-04-10 /pmc/articles/PMC9165498/ /pubmed/35398991 http://dx.doi.org/10.1002/advs.202103135 Text en © 2022 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Sun, Yang
Teng, Yan
Wang, Liyuan
Zhang, Zhaoying
Chen, ChaoJia
Wang, Yingchun
Zhang, Xiaodong
Xiang, Peng
Song, Xiaojia
Lu, Jinghui
Li, Nailin
Gao, Lifen
Liang, Xiaohong
Xia, Yuchen
Wu, Zhuanchang
Ma, Chunhong
LINC01431 Promotes Histone H4R3 Methylation to Impede HBV Covalently Closed Circular DNA Transcription by Stabilizing PRMT1
title LINC01431 Promotes Histone H4R3 Methylation to Impede HBV Covalently Closed Circular DNA Transcription by Stabilizing PRMT1
title_full LINC01431 Promotes Histone H4R3 Methylation to Impede HBV Covalently Closed Circular DNA Transcription by Stabilizing PRMT1
title_fullStr LINC01431 Promotes Histone H4R3 Methylation to Impede HBV Covalently Closed Circular DNA Transcription by Stabilizing PRMT1
title_full_unstemmed LINC01431 Promotes Histone H4R3 Methylation to Impede HBV Covalently Closed Circular DNA Transcription by Stabilizing PRMT1
title_short LINC01431 Promotes Histone H4R3 Methylation to Impede HBV Covalently Closed Circular DNA Transcription by Stabilizing PRMT1
title_sort linc01431 promotes histone h4r3 methylation to impede hbv covalently closed circular dna transcription by stabilizing prmt1
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165498/
https://www.ncbi.nlm.nih.gov/pubmed/35398991
http://dx.doi.org/10.1002/advs.202103135
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