ArticleJournal of virology2022
Hepatitis B Virus X Protein Expression Is Tightly Regulated by N6-Methyladenosine Modification of Its mRNA.
Article in Journal of virology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 35 citations in OpenAlex.
- HBx interacts with the host YBX3 protein and up-regulates its expression to mediate efficient Hepatitis B viral replication.Frontiers in cellular and infection microbiology · 2026Article
- Regulation of viral hepatitis by N6-methyladenosine RNA methylation.Emerging microbes & infections · 2025Review
- Article
- Hepatic steatosis and pyroptosis are induced by the hepatitis B virus X protein via B56α-METTL3 interaction-mediated m6A modification of the NLRP3 mRNA.Cell death & disease · 2025Article
- Epitranscriptomic Regulation of Hepatitis B Virus by RNA 5-Methylcytosine: Functions, Mechanisms, and Therapeutic Potential.Viruses · 2025Review
- The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions.MedComm · 2025Review
- Unveiling the dynamics and therapeutic potential of mInternational journal of biological sciences · 2025Review
- Article
- Past, Present, and Future of RNA Modifications in Infectious Disease Research.ACS infectious diseases · 2024Article
- Epigenetic modification of hepatitis B virus infection and related hepatocellular carcinoma.Virulence · 2024Review
- RNA Modifications in Pathogenic Viruses: Existence, Mechanism, and Impacts.Microorganisms · 2024Review
- Role of N6-methyladenosine RNA modification in cancer.MedComm · 2024Review
- Recent insights into NCurrent opinion in genetics & development · 2024Review
- 1mΨ influences the performance of various positive-stranded RNA virus-based replicons.Scientific reports · 2024Article
- Epitranscriptomic cytidine methylation of the hepatitis B viral RNA is essential for viral reverse transcription and particle production.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- [Post-transcriptional regulation mechanism and antiviral strategy of hepatitis B virus RNA].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024Review
- Review
- The Significance of N6-Methyladenosine RNA Methylation in Regulating the Hepatitis B Virus Life Cycle.Journal of microbiology and biotechnology · 2024Review
- Porcine alveolar macrophages host proteins interacting with African swine fever virus p72.Frontiers in microbiology · 2024Article
- Analysis of N6-Methyladenosine Modification of HBV RNA by Methylated RNA Immunoprecipitation.Methods in molecular biology (Clifton, N.J.) · 2024Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Hepatitis B virus (HBV) encodes a regulatory protein, termed HBx, that has been intensely studied in the past and shown to play a key role(s) in viral transcription and replication. In addition, a huge body of work exists in the literature related to signal transduction and possible mechanism(s) leading to hepatocarcinogenesis associated with infection. We have previously reported that HBV transcripts are modified by N6-methyladenosine (m6A) at the single consensus DRACH motif at nucleotides (nt) 1905 to 1909 in the epsilon structural element, and this m6A modification affects the HBV life cycle. In this study, we present evidence that additional variants of m6A (DRACH) motifs located within nt 1606 to 1809 correspond to the coding region of HBx mRNA and 3' untranslated region (UTR) of other viral mRNAs. Using the mutants of additional m6A sites in nt 1606 to 1809 and a depletion strategy of m6A methyltransferases (METTL3/14) and reader proteins (YTHDFs), we show that m6A modification at nt 1616, located in the HBx coding region, regulates HBx protein expression. The HBx RNA and protein expression levels were notably increased by the silencing of m6A reader YTHDF2 and methyltransferases as well as the mutation of m6A sites in the HBx coding region. However, other viral protein expression levels were not affected by the m6A modification at nt 1616. Thus, m6A modifications in the HBx open reading frame (ORF) downregulate HBx protein expression, commonly seen during HBV transfections, transgenic mice, and natural infections of human hepatocytes. These studies identify the functional role of m6A modification in the subtle regulation of HBx protein expression consistent with its possible role in establishing chronic hepatitis.
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