N6-methyladenosine and Its Implications in Viruses

Abstract

N⁶-methyladenine (m⁶A) is the most abundant RNA modification in mammalian messenger RNAs (mRNAs), which participates in and regulates many important biological activities, such as tissue development and stem cell differentiation. Due to an improved understanding of m⁶A, researchers have discovered that the biological function of m⁶A can be linked to many stages of mRNA metabolism and that m⁶A can regulate a variety of complex biological processes. In addition to its location on mammalian mRNAs, m⁶A has been identified on viral transcripts. m⁶A also plays important roles in the life cycle of many viruses and in viral replication in host cells. In this review, we briefly introduce the detection methods of m⁶A, the m⁶A-related proteins, and the functions of m⁶A. We also summarize the effects of m⁶A-related proteins on viral replication and infection. We hope that this review provides researchers with some insights for elucidating the complex mechanisms of the epitranscriptome related to viruses, and provides information for further study of the mechanisms of other modified nucleobases acting on processes such as viral replication. We also anticipate that this review can stimulate collaborative research from different fields, such as chemistry, biology, and medicine, and promote the development of antiviral drugs and vaccines.

Keywords: Eraser protein; Reader protein; Virus; Writer protein; m(6)A.

Figure 1

Schematic diagram of m⁶A detection method A. Schematic diagram of m⁶A-seq . The fragmented mRNA is enriched with m⁶A-antibody, and non-enriched RNA is used as control. The information containing m⁶A is obtained by comparing the sequenced fragments before and after enrichment with antibody. B. Schematic diagram of miCLIP . After the fragment mRNA was enriched with antibodies, UV cross-linking was carried out, and misincorporation or reverse transcription termination would occur near the cross-linking sites during reverse transcription. m⁶A, N⁶-methyladenine; IP, immunoprecipitation; m⁶A-seq, N⁶-methyladenine sequencing; MeRIP-seq, methylated RNA immunoprecipitation sequencing; miCLIP, m⁶A individual-nucleotide-resolution cross-linking and immunoprecipitation; UV, ultraviolet.