Abstract
Posttranscriptional modifications have been implicated in regulation of nearly all biological aspects of cellular RNAs, from stability, translation, splicing, nuclear export to localization. Chemical modifications also have been revealed for virus derived RNAs several decades before, along with the potential of their regulatory roles in virus infection. Due to the dynamic changes of RNA modifications during virus infection, illustrating the mechanisms of RNA epigenetic regulations remains a challenge. Nevertheless, many studies have indicated that these RNA epigenetic marks may directly regulate virus infection through antiviral innate immune responses. The present review summarizes the impacts of important epigenetic marks on viral RNAs, including N6-methyladenosine (m6A), 5-methylcytidine (m5C), 2ʹ-O-methylation (2ʹ-O-Methyl), and a few uncanonical nucleotides (A-to-I editing, pseudouridine), on antiviral innate immunity and relevant signaling pathways, while highlighting the significance of antiviral innate immune responses during virus infection.
Highlights
Chemical modifications of RNA, be designated as epitranscriptomic marks of RNA, are considered common features in most natural RNAs
Several studies indicate the important roles of TLRs that usually sense long double-strand RNAs (dsRNA) inside endolysosome or outside the cells in antiviral innate immune response, they have rarely been found to be regulated by RNA modifications, partly because many RNA viruses expose their genomic dsRNA in the cytoplasm (Akira et al, 2001; Alexopoulou et al, 2001; Heil et al, 2004)
Previous studies showed that IFN stimulated genes (ISG) generally functioned by interacting with different co-factors, mediating antiviral effects by promoting viral RNA degradation, abrogating viral proteins translation, or combining both (Nguyen et al, 2001; Bick et al, 2003; Yang and Li, 2020)
Summary
Chemical modifications of RNA, be designated as epitranscriptomic marks of RNA, are considered common features in most natural RNAs. Further investigation demonstrated that these negative effects might be induced by m6A related enzymes, including YTHDFs and METTLs. Instead of encoding innate immune antagonist proteins, m6A modifications in viral RNAs enable the recruitment of the m6A enzymes, which subsequently sequestrates viral ds/ssRNA through their RNA binding ability to prevent RIG-I recognition. Several studies indicate the important roles of TLRs that usually sense long dsRNA inside endolysosome or outside the cells in antiviral innate immune response, they have rarely been found to be regulated by RNA modifications, partly because many RNA viruses expose their genomic dsRNA in the cytoplasm (Akira et al, 2001; Alexopoulou et al, 2001; Heil et al, 2004).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
