A recent study published in Discovery of cell death summarized recent advances in the role of N6-methyladenosine (m6A) methylation in coronavirus disease 2019 (COVID-19).
Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, belongs to the Coronaviridae family and is closely related to SARS-CoV and Middle East respiratory syndrome (MERS)-CoV.
To date, COVID-19 has caused more than 769.7 million infections and 6.9 million deaths worldwide. meter6A is a common modification of ribonucleic acid (RNA) and plays crucial roles in several biological processes.
Recent evidence suggests that m6A methylation is associated with viral infections and affects host cell functions. In addition, it can also influence the life cycle and pathogenicity of viruses.
As such, understanding the role of m6A methylation during SARS-CoV-2 infection may help inform the prevention and treatment of COVID-19. In the present study, the authors reviewed the available evidence on m6A methylation and its role in COVID-19.
General description of m6TO
meter6A methylation is highly enriched for stop codons, long internal exons, and 3′ untranslated regions. It is catalyzed by methyltransferase-like 14 (METTL14) and METTL3. In addition, other proteins, including WT1-associated protein (WTAP) and RNA-binding motif protein 15 (RBM15), have been implicated in m6A methylation.
meter6Readers are proteins that recognize and bind to m.6A-modified RNA, such as insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), YTH N6 methyladenosine RNA-binding protein F1 (YTHDF1), heterogeneous nuclear ribonucleoprotein C (HNRNPC), YTHDF2, YTHDF3, YTH N6- methyladenosine RNA-binding protein C1 (YTHDC1) and YTHDC2. Demethylases are m6Some erasers that invert the m6A modification, such as AlkB homologue 5 RNA demethylase (ALKBH5).
COVID-19 and m6TO
The evidence suggests that m6A modification is vital for the transmission and pathogenicity of SARS-CoV-2. One study revealed dysregulation of m6A modification in host cells infected with SARS-CoV-2. Another study reported greater m6A levels in Calu-6 cells and Vero cells infected with SARS-CoV-2.
Besides m6Downregulation was observed in leukocytes from infected patients. Significant downregulation of METTL3 was observed in the lung tissues of severely ill COVID-19 patients compared to healthy individuals.
One study observed elevated expression of HNRNPC, WTAP, fragile X messenger ribonucleoprotein 1 (FMR1), RBM15, heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1), YTHDF3, YTHDC1, and ELAV-like RNA-binding protein 1 (ELAVL1) in COVID-19 patients. 19 patients. In contrast, the expression of insulin-like growth factor-binding protein 2 (IGFBP2), IGFB2BP1, and RBM15B was substantially reduced.
SARS-CoV-2 infection could alter the epigenetic transcriptome of m6A in lymphocytes and improve m6A modification of RBM15 to regulate immune responses. A study revealed the downregulation of METTL3 in host cells following SARS-CoV-2 infection, which decreases m6At levels in viral and host genes and enhances the expression of downstream inflammatory genes and innate immune responses.
impact of m6A change in the evolution of SARS-CoV-2
One study explored the methylation profiles in human and monkey cells infected with SARS-CoV-2 and revealed dynamic distribution patterns. He also observed a widespread occurrence of the modification in minus-strand RNAs. In addition, the researchers used more precise techniques and demonstrated eight m6Modification sites with single base resolution.
Functional analyzes indicated that METTL3, METTL14, and ALKBH5 regulated SARS-CoV-2 replication and that a reduction in m6One reader, YTHDF2, promoted replication and infectivity. In addition, SARS-CoV-2 can use host enzymes for methylation in order to adapt its DRACH sequence (D = A/G/U, R = A/G, H = A/C/U) and evade the interferons.
meter6A and diagnosis and treatment of COVID-19
The underlying mechanisms m6A methylation could be harnessed to develop prophylactic and therapeutic approaches for COVID-19. For example, a model designed to predict the risk of COVID-19 by detecting m6The A-associated genes were successful.
Similarly, another study reported highly accurate prediction of the occurrence of COVID-19 using randomized forest models. Therefore, the prediction models are expected to reveal the early onset and progression of COVID-19.
meter6A-related genes can be modified to reduce the virulence of SARS-CoV-2. That is, knockdown of YTHDF2, METTL14, and METTL3 elevated SARS-CoV-2 replication, while knockdown of ALKBH5 repressed it, suggesting that drugs against m6Regulators could be effective in dealing with COVID-19.
There are reports of small molecules targeting am6A regulators with antagonistic effects against other viruses. However, further investigation is warranted to detect m6Small A-related molecules that target SARS-CoV-2.
concluding remarks
Although m6A modification has been implied to be critical in COVID-19; further research is needed to unravel the underlying regulatory mechanisms. Additionally, research on m6The use of A-related small molecules that target SARS-CoV-2 is warranted. In general, a greater understanding of the role of m6The modifications of COVID-19 may lead to the development of new therapies in the future.
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