The Reversible Methylation of m6A Is Involved in Plant Virus Infection

Abstract

In recent years, m6A RNA methylation has attracted broad interest and is becoming a hot research topic. It has been demonstrated that there is a strong association between m6A and viral infection in the human system. The life cycles of plant RNA viruses are often coordinated with the mechanisms of their RNA modification. Here, we reviewed recent advances in m6A methylation in plant viruses. It appears that m6A methylation plays a dual role during viral infection in plants. On the one hand, m6A methylation acts as an antiviral immune response induced by virus infection, which inhibits viral replication or translation through the methylation of viral genome RNAs. On the other hand, plant viruses could disrupt the m6A methylation through interacting with the key proteins of the m6A pathway to avoid modification. Those plant viruses containing ALKB domain are discussed as well. Based on this mechanism, we propose that new strategies for plant virus control could be designed with competitive antagonists of m6A-associated proteins.

AlkB RNA demethylase homologues and N6‐methyladenosine are involved in Potyvirus infection

“…It has been known since the 1970s that m 6 A occurs in viral RNAs (Lavi & Shatkin, 1975; Yue et al, 2022; Zhang, Qian, et al, 2021), but advances in its detection and mapping are redefining our understanding of the roles of this modification in virus infection (Dang et al, 2019; Zhang, Qian, et al, 2021). Genetic manipulation of m 6 A writer or eraser levels has enabled the establishment of models in which m 6 A acts as a proviral modification that, for instance, promotes replication of influenza A virus (Courtney et al, 2017) and human immunodeficiency virus‐1 (Lichinchi, Gao, et al, 2016).…”

“…In plants, m 6 A functionally modulates a variety of processes including development and responses to biotic and abiotic stress (Zhou et al, 2022). Very recent reports support its involvement in plantvirus interaction (Yue et al, 2022). Enzymes of the alkylation B (AlkB) superfamily reverse m 6 A methylation (Fedeles et al, 2015), and AlkB domains are present within viral replication-associated proteins of plant RNA viruses in the families Closteroviridae, Alphaflexiviridae, Betaflexiviridae, and Secoviridae (Bratlie & Drabløs, 2005;Halgren et al, 2007;Moore & Meng, 2019).…”

Recent Acquisition of Functional m6A RNA Demethylase Domain in Orchid Ty3/Gypsy Elements

“…We can speculate that, upon translation, the RNA demethylase protein (ORF2), which is expressed independently of the Gag-Pol polyprotein (ORF1), could bind and be enzymatically active against the cognate TE mRNA or any cellular RNA. To bring any advantage to the TE, this could suppose either that the TE mRNA is subject to m6A methylation by the host and that it is deleterious to the TE replication cycle or/and that the demethylation of other cellular RNA by TE-encoded AlkB protein impacts the stability and translation of genes involved in different layers of TE control, as recently proposed for some AlkB-encoding plant RNA viruses ( Yue et al, 2022 ).…”

“…Interestingly, while alkbh9b knockout mutants do not show differences in overall plant RNA m6A methylation level, its depletion results in hypermethylation of alfalfa mosaic virus (AMV) RNA and impairment of systemic infection ( Martínez-Pérez et al, 2017 , 2021 ). In addition, several studies have pointed out the varying roles of m6A modifications in the life cycle of animal- and plant-infecting RNA viruses ( Gonzales-van Horn and Sarnow, 2017 ; Williams et al, 2019 ; Yue et al, 2022 ). More recently, RNA m6A methylation was also reported to play a role in the control of the replication of mammalian endogenous viruses and retrotransposons elements in contrasting ways.…”

Transcriptome-wide analyses of RNA m6A methylation in hexaploid wheat reveal its roles in mRNA translation regulation

“…In recent years, many studies have enhanced our understanding of the roles of m6A methylation in plants. There are lines of evidence suggesting that the m6A methylation of mRNAs are widely engaged in various processes of plants, including embryo development ( Zhong et al, 2008 ; Bodi et al, 2012 ), photosynthesis ( Luo et al, 2014 ; Wan et al, 2015 ), callus induction ( Li et al, 2014 ; Du et al, 2020 ), as well as responses to biotic or abiotic stresses ( Bai et al, 2021 ; Cheng et al, 2021 ; Zhang et al, 2021 ; Yue et al, 2022 ). For example, the knock-out of a mRNA adenosine methylase (MTA) gene in Arabidopsis resulted in the inhibition of m6A methylation and the failure of embryo development ( Zhong et al, 2008 ).…”