ArticlePLoS pathogens2023
NSUN2-mediated m5C modification of HBV RNA positively regulates HBV replication.
Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 48 citations in OpenAlex.
- NSUN2-FOSB reciprocity facilitates leukemogenesis in an mHaematologica · 2026Article
- NSUN2‑mediated epitranscriptomic and ubiquitin modulation of Nipah virus matrix protein reveals a dual-targeting antiviral strategy.Protein & cell · 2026Article
- Mechanism study of RUNX1/NSUN2 upregulating fatty acid-binding protein 5 through 5-methylcytosine methylation to mediate lipid metabolic reprogramming to promote immunotherapy resistance in non-small cell lung cancer.Respiratory research · 2026Article
- Hepatitis B virus promotes hepatocellular carcinoma progression by disrupting NSUN2/YBX1-mediated mVirologica Sinica · 2026Article
- Global research trends on the relationship between RNA mBiophysics reports · 2026Article
- m5C RNA methylation is dysregulated by oncogenic herpesviruses via c-Myc signaling to counteract host antiviral factors.Nucleic acids research · 2026Article
- Enhancing plant antiviral responses and productivity through the elimination of mScience advances · 2026Article
- m5c-modified LINC01094 participates in epithelial-mesenchymal transition and metastasis of cervical cancer cells via the ZNF582-SIRT1/p53 axis.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- Emerging roles of tRNA modification-mediated codon-specific translational reprogramming in cancer biology.Cell death & disease · 2026Review
- NSUN2-Mediated mInternational journal of general medicine · 2026Review
- RNA epitranscriptomic regulation of tumor immune evasion: mechanisms, context-dependent roles, and therapeutic implications.Frontiers in immunology · 2026Review
- m5C: Novel Diagnostic and Drug Repurposing Targets for Nonalcoholic Steatohepatitis.International journal of genomics · 2026Article
- NSUN5 and RNA mFrontiers in cell and developmental biology · 2026Review
- NSUNs-driven dysregulation: the next frontier in targeted cancer therapy?Cell death & disease · 2025Review
- Flaviviridae RdRp exploits NSUN2-driven m5C methylation to establish persistent infection.PLoS pathogens · 2025Article
- The Role of NSUN Family Genes in m5C Methylation and Diseases.Biomedicines · 2025Review
- Analysis of the Porcine Reproductive and Respiratory Syndrome Virus Nucleocapsid Interactome.Journal of proteome research · 2025Article
- RNA methylation in hepatocellular carcinoma: from metabolic reprogramming and immune escape mechanisms to small molecule inhibitor development.Journal of translational medicine · 2025Review
- Epitranscriptomic Regulation of Hepatitis B Virus by RNA 5-Methylcytosine: Functions, Mechanisms, and Therapeutic Potential.Viruses · 2025Review
- NSUN2-mediated HCV RNA m5C Methylation Facilitates Viral RNA Stability and Replication.Genomics, proteomics & bioinformatics · 2025Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic hepatitis B virus (HBV) infection is a major cause of liver cirrhosis and liver cancer, despite strong prevention and treatment efforts. The study of the epigenetic modification of HBV has become a research hotspot, including the N6-methyladenosine (m6A) modification of HBV RNA, which plays complex roles in the HBV life cycle. In addition to m6A modification, 5-methylcytosine (m5C) is another major modification of eukaryotic mRNA. In this study, we explored the roles of m5C methyltransferase and demethyltransferase in the HBV life cycle. The results showed that m5C methyltransferase NSUN2 deficiency could negatively regulate the expression of HBV while m5C demethyltransferase TET2 deficiency positively regulates the expression of HBV. Subsequently, we combined both in vitro bisulfite sequencing and high-throughput bisulfite sequencing methods to determine the distribution and stoichiometry of m5C modification in HBV RNA. Two sites: C2017 and C131 with the highest-ranking methylation rates were identified, and mutations at these two sites could lead to the decreased expression and replication of HBV, while the mutation of the "fake" m5C site had no effect. Mechanistically, NSUN2-mediated m5C modification promotes the stability of HBV RNA. In addition, compared with wild-type HepG2-NTCP cells and primary human hepatocytes, the replication level of HBV after NSUN2 knockdown decreased, and the ability of the mutant virus to infect and replicate in wild-type HepG2-NTCP cells and PHHs was substantially impaired. Similar results were found in the experiments using C57BL/6JGpt-Nsun2+/- mice. Interestingly, we also found that HBV expression and core protein promoted the endogenous expression of NSUN2, which implied a positive feedback loop. In summary, our study provides an accurate and high-resolution m5C profile of HBV RNA and reveals that NSUN2-mediated m5C modification of HBV RNA positively regulates HBV replication by maintaining RNA stability.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.