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Updated: Mar 7, 2026

Exploring m6A and m5C Epitranscriptomes upon Viral Infection: an Example with HIV
Published on: March 5, 2022
Viral Epitranscriptomics
Edward M Kennedy1, David G Courtney1, Kevin Tsai1
1Department of Molecular Genetics and Microbiology and Center for Virology, Duke University Medical Center, Durham, North Carolina, USA.
Abstract:
Although it has been known for over 40 years that eukaryotic mRNAs bear internal base modifications, it is only in the last 5 years that the importance of these modifications has begun to come into focus. The most common mRNA modification, the addition of a methyl group to the N6 position of adenosine (m6A), has been shown to affect splicing, translation, and stability, and m6A is also essential for embryonic development in organisms ranging from plants to mice. While all viral transcripts examined so far have been found to be extensively m6A modified, the role, if any, of m6A in regulating viral gene expression and replication was previously unknown. However, recent data generated using HIV-1 as a model system strongly suggest that sites of m6A addition not only are evolutionarily conserved but also enhance virus replication. It is therefore likely that the field of viral epitranscriptomics, which can be defined as the study of functionally relevant posttranscriptional modifications of viral RNA transcripts that do not change the nucleotide sequence of that RNA, is poised for a major expansion in scientific interest and may well fundamentally change our understanding of how viral replication is regulated.
Insights
The N6-methyladenosine (m6A) modification in RNA, crucial for cellular processes, is now shown to enhance HIV-1 replication. This finding opens the door to understanding viral epitranscriptomics and its role in virus regulation.
Area of Science:
- Molecular Biology
- Virology
- Epigenetics
Background:
- Eukaryotic mRNAs undergo internal base modifications, with N6-methyladenosine (m6A) being the most common.
- m6A modifications are known to influence splicing, translation, and mRNA stability, and are vital for embryonic development.
- While viral transcripts are extensively m6A modified, its role in viral gene expression and replication remained unclear.
Purpose of the Study:
- To investigate the role of m6A modifications in regulating viral gene expression and replication.
- To explore the potential significance of m6A in viral epitranscriptomics using HIV-1 as a model.
Main Methods:
- Analysis of m6A modification sites in viral transcripts.
- Functional studies using HIV-1 to assess the impact of m6A on replication.
Main Results:
- m6A modification sites in HIV-1 transcripts are evolutionarily conserved.
- m6A modifications were found to enhance HIV-1 replication.
Conclusions:
- m6A plays a significant role in regulating viral replication.
- The field of viral epitranscriptomics is poised for expansion, potentially transforming our understanding of viral regulation.
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