N6-Methyladenosine and Viral Infection

Abstract

N⁶-methyladenosine (m⁶A), as a dynamic posttranscriptional RNA modification, recently gave rise to the field of viral epitranscriptomics. The interaction between virus and host is affected by m⁶A. Multiple m⁶A-modified viral RNAs have been observed. The epitranscriptome of m⁶A in host cells are altered after viral infection. The expression of viral genes, the replication of virus and the generation of progeny virions are influenced by m⁶A modifications in viral RNAs during virus infection. Meanwhile, the decorations of m⁶A in host mRNAs can make viral infections more likely to happen or can enhance the resistance of host to virus infection. However, the mechanism of m⁶A regulation in viral infection and host immune response has not been thoroughly elucidated to date. With the development of sequencing-based biotechnologies, transcriptome-wide mapping of m⁶A in viruses has been achieved, laying the foundation for expanding its functions and corresponding mechanisms. In this report, we summarize the positive and negative effects of m⁶A in distinct viral infection. Given the increasingly important roles of m⁶A in diverse viruses, m⁶A represents a novel potential target for antiviral therapy.

Keywords: immune; infection; m6A; viral life cycle; virus.

Figure 1

Related mechanisms and functions of m⁶A modification in mRNAs. The m⁶A modification is regulated by the “writers,” “erasers,” “readers” and “anti-readers.” Writers are composed of METTL3, METTL14, WTAP, KIAA1429, ZC3H13, RBM15, and METTL16, which have been reported to induce m⁶A RNA methylation. Erasers are m⁶A demethylases including FTO and ALKBH5. Readers are proteins that bind to m⁶A modified mRNAs and play corresponding roles. Those proteins that have been identified as readers to date include YTHDF1, YTHDF2, YTHDF3, YTHDC1, YTHDC2, eIF3, IGF2BP1, IGF2BP2, IGF2BP3, FMRP, and hnRNPA2/B1. The functions of m⁶A are related to almost all stages in deciding the fate of mRNAs including pre-mRNA splicing, pri-miRNA processing, mRNA export, mRNA stability, translation modulation and mRNA degradation. Anti-readers are proteins that preferentially bind to mRNAs in the absence of m⁶A, such as G3BP1/2, CAPRIN1, USP10, and RBM42.