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Review
. 2023 Oct 17:14:1286820.
doi: 10.3389/fimmu.2023.1286820. eCollection 2023.

The regulation of antiviral innate immunity through non-m6A RNA modifications

Shenghai Shen  1 , Li-Sheng Zhang  1   2
Affiliations
Review

The regulation of antiviral innate immunity through non-m6A RNA modifications

Shenghai Shen et al. Front Immunol. .

Abstract

The post-transcriptional RNA modifications impact the dynamic regulation of gene expression in diverse biological and physiological processes. Host RNA modifications play an indispensable role in regulating innate immune responses against virus infection in mammals. Meanwhile, the viral RNAs can be deposited with RNA modifications to interfere with the host immune responses. The N6-methyladenosine (m6A) has boosted the recent emergence of RNA epigenetics, due to its high abundance and a transcriptome-wide widespread distribution in mammalian cells, proven to impact antiviral innate immunity. However, the other types of RNA modifications are also involved in regulating antiviral responses, and the functional roles of these non-m6A RNA modifications have not been comprehensively summarized. In this Review, we conclude the regulatory roles of 2'-O-methylation (Nm), 5-methylcytidine (m5C), adenosine-inosine editing (A-to-I editing), pseudouridine (Ψ), N1-methyladenosine (m1A), N7-methylguanosine (m7G), N6,2'-O-dimethyladenosine (m6Am), and N4-acetylcytidine (ac4C) in antiviral innate immunity. We provide a systematic introduction to the biogenesis and functions of these non-m6A RNA modifications in viral RNA, host RNA, and during virus-host interactions, emphasizing the biological functions of RNA modification regulators in antiviral responses. Furthermore, we discussed the recent research progress in the development of antiviral drugs through non-m6A RNA modifications. Collectively, this Review conveys knowledge and inspiration to researchers in multiple disciplines, highlighting the challenges and future directions in RNA epitranscriptome, immunology, and virology.

Keywords: 2’-O-methyltransferase; 5-methylcytidine; RNA editing; RNA modification; innate immunity; pseudouridine; virus infection.

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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
Structures of major non-m6A RNA modifications in mammals.
Figure 2
Figure 2
Functional roles of Nm in the regulation of antiviral innate immunity.
Figure 3
Figure 3
Functional roles of RNA m5C in the regulation of antiviral innate immunity.
Figure 4
Figure 4
Functional roles of ADAR and A-to-I editing in the regulation of antiviral innate immunity.
Figure 5
Figure 5
Functional roles of pseudouridine (Ψ) in the regulation of antiviral innate immunity.
See this image and copyright information in PMC

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