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N⁶-methyladenosine modification-a key player in viral infection.

ABSTRACT: N⁶-methyladenosine (m⁶A) modification is a dynamic, reversible process and is the most prevalent internal modification of RNA. This modification is regulated by three protein groups: methyltransferases ("writers"), demethylases ("erasers"), and m⁶A-binding proteins ("readers"). m⁶A modification and related enzymes could represent an optimal strategy to deepen the epigenetic mechanism. Numerous reports have suggested that aberrant modifications of m⁶A lead to aberrant expression of important viral genes. Here, we review the role of m⁶A modifications in viral replication and virus-host interactions. In particular, we focus on DNA and RNA viruses associated with human diseases, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV)-1, Epstein-Barr virus (EBV), and Kaposi's sarcoma-associated herpesvirus (KSHV). These findings will contribute to the understanding of the mechanisms of virus-host interactions and the design of future therapeutic targets for treatment of tumors associated with viral infections.

SUBMITTER: Zhang X

PROVIDER: S-EPMC10571408 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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N6-methyladenosine modification-a key player in viral infection.

Zhang Xiaoyue X Peng Qiu Q Wang Lujuan L

Cellular & molecular biology letters 20231012 1

N6-methyladenosine (m6A) modification is a dynamic, reversible process and is the most prevalent internal modification of RNA. This modification is regulated by three protein groups: methyltransferases ("writers"), demethylases ("erasers"), and m6A-binding proteins ("readers"). m6A modification and related enzymes could represent an optimal strategy to deepen the epigenetic mechanism. Numerous reports have suggested that aberrant modifications of m<sup ...[more]

PMID: 37828480

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Project description:BackgroundRespiratory syncytial virus (RSV) is the second leading cause of death due to lower respiratory tract infections. Effective prevention and treatment measures are lacking, posing a huge socioeconomic burden to the world. N 6-methyladenosine (m6A) is the most common internal modification in messenger RNA and noncoding RNA. Numerous recent studies have shown that the dysregulation of m6A modification is associated with diseases caused by pathogenic viruses.MethodsThe changes in m6A modification were evaluated using m6A RNA methylation assay. The differences in gene expression levels of various m6A-modifying enzymes were observed using Quantitative Real-time PCR (qRT-PCR) during RSV infection. The autophagosomes were observed using transmission electron microscopy, and the expression of autophagy-associated protein Microtubule Associated Protein 1 Light Chain 3 Beta Ⅱ/Ⅰ (LC3B Ⅱ/Ⅰ) and Beclin1 in Human Normal Lung Epithelial Cells (BEAS-2B) cells using Western blot during RSV infection. The significantly differentially expressed genes were screened guided by bioinformatics. Their relationship with m6A-modifying enzymes was analyzed through protein-protein interaction network and expression correlation analysis.ResultsThe m6A abundance decreased and demethylase Fat Mass and Obesity- Associated Protein (FTO) significantly increased during RSV infection after 24 h. We also found that the DNA Damage-Inducible Transcript 3 Protein (DDIT3) level significantly increased during RSV infection after 24 h and observed autophagosomes in BEAS-2B cells. In addition, RSV infection could cause the upregulation of LC3B Ⅱ/Ⅰ and Beclin1. The expression correlation analysis showed that DDIT3 levels were positively correlated with the FTO level, and Methyltransferase Like 3 (METTL3), RNA Binding Motif Protein 15B (RBM15B), YTH Domain-Containing Family Protein 1 (YTHDF1), and levels were negatively correlated with the DDIT3 level.ConclusionsWe uncovered a significant role for m6A modification during RSV infection. Also, a correlation was found between m6A and autophagy, providing new ideas for therapeutic advancements in RSV treatment.

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N⁶-methyladenosine modification-a key player in viral infection.

Publications

N<sup>6</sup>-methyladenosine modification-a key player in viral infection.

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