Emerging roles of biological m 6 A proteins in regulating virus infection: A review.

N ⁶ -methyladenosine (m ⁶ A) is the most prevalent chemical modifications of intracellular RNA, which recently emerging as a multifaceted effector of viral genomic RNA. As a dynamic process, three groups of biological proteins control the levels of m ⁶ A modification in eukaryocyte, designed as m ⁶ A writers, erasers, and readers. The m ⁶ A writers comprising of methyltransferases complex initiate the modification process. On the contrary, the m ⁶ A erasers ALKBH5 or FTO abolish the modification through three-step demethylation: m ⁶ A to N ⁶ -hydroxymethyl adenosine (hm ⁶ A), then hm ⁶ A to N ⁶ -methyladenosine (f ⁶ A), and finally f ⁶ A to adenosine. The known m ⁶ A readers include the YTH family and the hnRNP family. As m ⁶ A modification regulates RNA nuclear exportation, stability, and translation, m ⁶ A proteins commonly participate in virus infection by regulating viral genomic RNA synthesis. Moreover, m ⁶ A proteins establish molecular linkages between virus genome/viral encode proteins and host cells proteins via their multifunctional roles in cellular RNA metabolism. The m ⁶ A writers and erasers directly impact interferon expression and macrophage innate immune responses, facilitating them to act as anti-/pro-viral factors. The m ⁶ A readers enable to alter cell metabolism and stress granules (SGs) production to regulate virus-host interactions. Here, the latest progress of m ⁶ A proteins in regulating viral infection is reviewed. Demonstrating the roles of m ⁶ A proteins will enhance the understanding of epigenetic regulation of virus infection and stimulate the development of novel antiviral strategies.
Competing Interests: Declaration of competing interest All the authors claim no conflict of interest.
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