N6-methyladenosine modifications enhance enterovirus 71 ORF translation through METTL3 cytoplasmic distribution

Methyltransferase-like 3 Modulates Severe Acute Respiratory Syndrome Coronavirus-2 RNA N6-Methyladenosine Modification and Replication

“…The m 6 A methyltransferases and demethylases are mainly localized in the nucleus. Infection by viruses that replicate in the cytoplasm, such as enterovirus 71 (EV71), HCV, ZIKV, and porcine epidemic diarrhea virus (PEDV), affects the expression and localization of methyltransferases and demethylases to facilitate their RNA m 6 A modifications, which influences viral replication ( 37 , 38 , 50 – 52 ). To check whether SARS-CoV-2 infection had a similar effect, SARS-CoV-2-infected Vero E6 cells were harvested.…”

“…m 6 A modification has been identified in RNA viruses replicating in both the nucleus and the cytoplasm ( 5 , 9 , 54 ) and has different regulation mechanisms. Similar to the RNA viruses influenza A virus (IAV), human immunodeficiency virus (HIV), and enterovirus 71 (EV71) ( 40 , 42 , 50 , 51 ), the m 6 A modification of SARS-CoV-2 promotes virus replication in Vero E6 cells, which is different from the result of SARS-CoV-2 infection in Huh7 cells ( 47 ). The m 6 A modification of viral RNAs attenuates host innate immunity via RIG-I signaling in virus infection, indicating that the interferon pathway is linked to the viral m 6 A modification ( 55 – 57 ).…”

Regulatory effect of m6A modification on different viruses

“…In addition, METTL3 depended on the binding of the nuclear transporter and its nuclear localization signal (NLS) for nuclear transport, while EV71 2A could competitively interact with METTL3 to bind to the nuclear transporter, thus regulating the cellular localization of METTL3 and locating it in the cytoplasm to enhance 2A expression. 83 These two pieces of research describe the mechanism by which the interaction between METTL3 and viral proteins promotes viral replication. The relationship of m 6 A with downstream host proteins involved in viral replication has not been reported, and there is a lot of room for exploration.…”

Regulation of Antiviral Immune Response by N6-Methyladenosine of mRNA

“…As a result, the increased METTL14 level facilitates EBV proliferation and self-renewal of host cells. Investigations show that the interaction between METTL3 and enterovirus 71 (EV71) nonstructural protein 2C or 3D may contribute to the cytoplasm localization of METTL3 in rhabdomyosarcoma (RD) cells ( Hao et al, 2019 ; Yao et al, 2020 ). In addition, the viral protein 2A that harbors a nuclear localization signal could compete with METTL3 for nuclear importing protein karyopherin, and this partially explains the redistribution of METTL3 after EV71 infection.…”