Recent insights into N6-methyladenosine during viral infection

Abstract

The RNA modification of N⁶-methyladenosine (m⁶A) controls many aspects of RNA function that impact biological processes, including viral infection. In this review, we highlight recent work that shapes our current understanding of the diverse mechanisms by which m⁶A can regulate viral infection by acting on viral or cellular mRNA molecules. We focus on emerging concepts and understanding, including how viral infection alters the localization and function of m⁶A machinery proteins, how m⁶A regulates antiviral innate immunity, and the multiple roles of m⁶A in regulating specific viral infections. We also summarize the recent studies on m⁶A during SARS-CoV-2 infection, focusing on points of convergence and divergence. Ultimately, this review provides a snapshot of the latest research on m⁶A during viral infection.

Figure 1.. m⁶A-methyltransferase complex localization and function can be regulated by viral infection.

A) m⁶A is added to nascent mRNA in the nucleus by the METTL3-METTL14-WTAP m⁶A-methyltransferase complex. B) The HSV-1 ICP27 protein exports the m⁶A-methyltransferase complex proteins METTL3 and METTL14 from the nucleus, decreasing both viral and cellular RNA m⁶A-modification. C) The Ebola virus VP30 protein alters the localization of the m⁶A-methyltransferase complex to modify viral RNA in the cytoplasm. D) Zika virus recruits the metabolic enzyme AHCY to viral replication factories indirectly leading to m⁶A-modification of the viral RNA by the m⁶A-methyltransferase complex. See text for more details.

Figure 2.. m⁶A regulates RNA binding protein interaction with viral or cellular RNA to impact viral infection.

These panels indicate diverse roles of m⁶A during viral infection that can act on viral or cellular RNA to either promote (A) or inhibit (B) viral infection. See the text for more details.