Study explores the role of N6-methyladensoine methylation and COVID-19

A recent study published in Cell Death Discovery summarized the recent advances in the role of N6-methyladenosine (m6A) methylation in coronavirus disease 2019 (COVID-19).

m6A methylation: a potential key player in understanding and treating COVID-2019 infection
Study: m6A methylation: a potential key player in understanding and treating COVID-2019 infection. Image Credit: felipe caparros/Shutterstock.com

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal 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. m6A is a common ribonucleic acid (RNA) modification and plays crucial roles in several biological processes.

Recent evidence suggests that m6A methylation is associated with viral infections and impacts host cellular functions. Besides, it can also influence the life cycle and pathogenicity of viruses.

As such, understanding the role of m6A methylation during SARS-CoV-2 infection can help inform COVID-19 prevention and treatment. In the present study, the authors reviewed available evidence on m6A methylation and its role in COVID-19.

Overview of m6A

m6A methylation is highly enriched in the stop codons, long internal exons, and 3’-untranslated regions. It is catalyzed by methyltransferase-like 14 (METTL14) and METTL3. Besides, other proteins, including the WT1-associated protein (WTAP) and RNA-binding motif protein 15 (RBM15), have been implicated in m6A methylation.

m6A readers are proteins recognizing and binding to m6A-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 m6A erasers that reverse the m6A modification, such as AlkB homolog 5 RNA demethylase (ALKBH5).

COVID-19 and m6A

Evidence suggests that m6A modification is vital for SARS-CoV-2 transmission and pathogenicity. One study revealed the de-regulation of m6A modification in SARS-CoV-2-infected host cells. Another study reported higher m6A levels in SARS-CoV-2-infected Calu-6 cells and Vero cells.

Further, m6A downregulation was observed in leucocytes from infected patients. Significant downregulation of METTL3 was observed in the lung tissues of severe COVID-19 patients relative 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. 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 enhance m6A modification of RBM15 to regulate immune responses. A study revealed the downregulation of METTL3 in host cells upon SARS-CoV-2 infection, decreasing m6A levels in host and viral genes and enhancing the expression of downstream inflammatory genes and innate immune responses.

Impact of m6A modification on SARS-CoV-2 evolution

One study explored methylation profiles in monkey and human cells infected with SARS-CoV-2 and revealed the dynamic distribution patterns. It also observed widespread occurrence of the modification on negative-strand RNAs. Moreover, the investigators used more precise techniques and demonstrated eight m6A modification sites at single-base resolution.

Functional analyses indicated that METTL3, METTL14, and ALKBH5 regulated SARS-CoV-2 replication and that a reduction in m6A reader, YTHDF2, promoted replication and infectivity. Moreover, SARS-CoV-2 can use host enzymes for methylation to adapt its DRACH sequence (D = A/G/U, R = A/G, H = A/C/U) and evade interferons.

m6A and COVID-19 diagnosis and treatment

The mechanisms underlying m6A methylation could be leveraged to develop prophylactic and therapeutic approaches for COVID-19. For instance, a model designed to predict COVID-19 risk by screening m6A-associated genes was successful.

Similarly, another study reported highly accurate prediction of COVID-19 occurrence using random forest models. Thus, prediction models are expected to reveal the early onset and progression of COVID-19.

m6A-related genes can be modified to reduce SARS-CoV-2 virulence. That is, knocking down YTHDF2, METTL14, and METTL3 elevated SARS-CoV-2 replication, whereas ALKBH5 knockdown repressed it, suggesting that drugs against m6A regulators could be effective in COVID-19 treatment.

There are reports of small molecules targeting m6A regulators with antagonistic effects against other viruses. However, additional research is warranted to screen m6A-related small molecules targeting SARS-CoV-2.

Concluding remarks

Although m6A modification has been implicated as critical in COVID-19, further investigations are necessary to unravel the underlying regulatory mechanisms. Additionally, research on m6A-related small molecules targeting SARS-CoV-2 is warranted. Overall, an increased understanding of the role of m6A modifications in COVID-19 may result in the development of novel therapies in the future.

Journal reference:
Tarun Sai Lomte

Written by

Tarun Sai Lomte

Tarun is a writer based in Hyderabad, India. He has a Master’s degree in Biotechnology from the University of Hyderabad and is enthusiastic about scientific research. He enjoys reading research papers and literature reviews and is passionate about writing.

Citations

Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Sai Lomte, Tarun. (2023, August 23). Study explores the role of N6-methyladensoine methylation and COVID-19. News-Medical. Retrieved on October 12, 2024 from https://www.news-medical.net/news/20230823/Study-explores-the-role-of-N6-methyladensoine-methylation-and-COVID-19.aspx.

  • MLA

    Sai Lomte, Tarun. "Study explores the role of N6-methyladensoine methylation and COVID-19". News-Medical. 12 October 2024. <https://www.news-medical.net/news/20230823/Study-explores-the-role-of-N6-methyladensoine-methylation-and-COVID-19.aspx>.

  • Chicago

    Sai Lomte, Tarun. "Study explores the role of N6-methyladensoine methylation and COVID-19". News-Medical. https://www.news-medical.net/news/20230823/Study-explores-the-role-of-N6-methyladensoine-methylation-and-COVID-19.aspx. (accessed October 12, 2024).

  • Harvard

    Sai Lomte, Tarun. 2023. Study explores the role of N6-methyladensoine methylation and COVID-19. News-Medical, viewed 12 October 2024, https://www.news-medical.net/news/20230823/Study-explores-the-role-of-N6-methyladensoine-methylation-and-COVID-19.aspx.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Fibrin fuels thromboinflammation and brain damage in COVID-19