Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Dec 13:13:1031200.
doi: 10.3389/fimmu.2022.1031200. eCollection 2022.

N6-methyladenosine modification of viral RNA and its role during the recognition process of RIG-I-like receptors

Huanan Li  1   2   3   4 , Yang Guo  1   2   3   4 , Wenbao Qi  1   2   3   4   5 , Ming Liao  1   2   3   4   5   6
Affiliations
Review

N6-methyladenosine modification of viral RNA and its role during the recognition process of RIG-I-like receptors

Huanan Li et al. Front Immunol. .

Abstract

N6-methyladenosine (m6A) is the most abundant RNA chemical modification in eukaryotes and is also found in the RNAs of many viruses. In recent years, m6A RNA modification has been reported to have a role not only in the replication of numerous viruses but also in the innate immune escape process. In this review, we describe the viruses that contain m6A in their genomes or messenger RNAs (mRNAs), and summarize the effects of m6A on the replication of different viruses. We also discuss how m6A modification helps viral RNAs escape recognition by exogenous RNA sensors, such as retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), during viral invasion. Overall, the goal of our review is to summarize how m6A regulates viral replication and facilitates innate immune escape. Furthermore, we elaborate on the potential of m6A as a novel antiviral target.

Keywords: RIG-I-like receptors; innate immune escape; m6A; replication; viruses.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Introduction of m6A modifications. (A) M6A is one of the first identified and most abundant internal modifications in the mRNA of eukaryotic cells. (B) M6A is a reversible chemical modification in RNAs; ‘writers’ add a methyl to the N6 position of adenosine; ‘erasers’ remove the methyl of m6A; after adding m6A in RNAs, ‘readers’ recognize the modified RNAs and regulate the biological process of RNAs, including translation, decay, and translocation.
Figure 2
Figure 2
M6A modifications of viral RNAs during the replication process of DNA viruses. DNA viruses produce mRNAs during replication. The viral mRNAs can be m6A modified, and these modifications can modulate the replication of DNA viruses.
Figure 3
Figure 3
M6A modifications of viral RNAs during the replication process of cytoplasmic RNA viruses. Some of the cytoplasmic RNA viruses possess a positive RNA genome, whereas some possess a negative RNA genome. Cytoplasmic RNA viruses can produce mRNA (the positive-sense RNA genome of cytoplasmic RNA viruses functions as mRNA) and cRNA. M6A is present in the viral genome RNA, cRNA, and mRNA, and can modulate viral protein expression and viral replication. ‘Writers’ and ‘erasers’ can translocate from the nucleus to the cytoplasm after viral infection.
Figure 4
Figure 4
M6A modifications of viral RNAs during the replication process of intranuclear RNA viruses. After binding to the receptors, the genome of intranuclear virus enters the nucleus, where replication and transcription occur. M6A is present in the viral genome RNA, cRNA, and mRNA. Both RNA translocation and mRNA translation are modulated by m6A modification.
Figure 5
Figure 5
M6A modifications of viral RNAs during the replication process of retroviruses. Retroviruses possess an RNA genome and have reverse transcription activity. M6A is present in both genomic RNA and mRNA of retroviruses, and plays roles in reverse transcription, RNA transcription, and mRNA translation.
Figure 6
Figure 6
M6A modifications of viral RNAs and their function in RLR sensing. Viral RNAs can form complicated secondary structures, and RLRs can recognize the double-stranded component. Adding m6A to viral RNAs can reshape RNA structure and enable viral RNAs to escape RLR recognition.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Desrosiers R, Friderici K, Rottman F. Identification of methylated nucleosides in messenger RNA from novikoff hepatoma cells. Proc Natl Acad Sci USA (1974) 71(10):3971–5. doi: 10.1073/pnas.71.10.3971 - DOI - PMC - PubMed
    1. Bokar JA, Rath-Shambaugh ME, Ludwiczak R, Narayan P, Rottman F. Characterization and partial purification of mRNA N6-adenosine methyltransferase from HeLa cell nuclei. internal mRNA methylation requires a multisubunit complex. J Biol Chem (1994) 269(26):17697–704. doi: 10.1016/s0021-9258(17)32497-3 - DOI - PubMed
    1. Bokar JA, Shambaugh ME, Polayes D, Matera AG, Rottman FM. Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase. RNA (1997) 3(11):1233–47. - PMC - PubMed
    1. Fu Y, Dominissini D, Rechavi G, He C. Gene expression regulation mediated through reversible m(6)A RNA methylation. Nat Rev Genet (2014) 15(5):293–306. doi: 10.1038/nrg3724 - DOI - PubMed
    1. Meyer KD, Jaffrey SR. The dynamic epitranscriptome: N6-methyladenosine and gene expression control. Nat Rev Mol Cell Biol (2014) 15(5):313–26. doi: 10.1038/nrm3785 - DOI - PMC - PubMed

Publication types

LinkOut - more resources