Next Article in Journal
Evolution of Cherries (Prunus Subgenus Cerasus) Based on Chloroplast Genomes
Next Article in Special Issue
Genomic and Metabolic Characterization of Plant Growth-Promoting Rhizobacteria Isolated from Nodules of Clovers Grown in Non-Farmed Soil
Previous Article in Journal
Exploiting the Features of Short Peptides to Recognize Specific Cell Surface Markers
Previous Article in Special Issue
Characterization of the Pyrroloquinoline Quinone Producing Rhodopseudomonas palustris as a Plant Growth-Promoting Bacterium under Photoautotrophic and Photoheterotrophic Culture Conditions
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
IJMS
Volume 24
Issue 21
10.3390/ijms242115608
ijms-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

The Roles of N6-Methyladenosine Modification in Plant–RNA Virus Interactions

by
Min He
1,2,
Zhiqiang Li
2 and
Xin Xie
1,*
1
Laboratory of Agricultural Microbiology, College of Agriculture, Guizhou University, Guiyang 550025, China
2
State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(21), 15608; https://doi.org/10.3390/ijms242115608
Submission received: 7 September 2023 / Revised: 6 October 2023 / Accepted: 20 October 2023 / Published: 26 October 2023
(This article belongs to the Special Issue Molecular Plant-Microbe Interactions 2.0)
Browse Figure
Versions Notes

Abstract

:
N6-methyladenosine (m6A) is a dynamic post-transcriptional RNA modification. Recently, its role in viruses has led to the study of viral epitranscriptomics. m6A has been observed in viral genomes and alters the transcriptomes of both the host cell and virus during infection. The effects of m6A modifications on host plant mRNA can either increase the likelihood of viral infection or enhance the resistance of the host to the virus. However, to date, the regulatory mechanisms of m6A in viral infection and host immune responses have not been fully elucidated. With the development of sequencing-based biotechnologies, the study of m6A in plant viruses has received increasing attention. In this mini review, we summarize the positive and negative consequences of m6A modification in different RNA viral infections. Given its increasingly important roles in multiple viruses, m6A represents a new potential target for antiviral defense.
Keywords:
m6A; RNA virus; infection; plant

1. Introduction

There are currently more than 150 known types of RNA modification. The most widespread type of RNA modification is methylation including N6-methyladenosine (m6A), 5-methylcytosine (m5C), N7-methylguanosine (m7A), and N1-methyladenosine (m1A) [1]. m6A is a type of methylation that occurs on the N-atom at the sixth position of adenine (A) bases [2]. The underlying methylation reaction, which affects almost every stage of mRNA metabolism [3], represents the most prevalent internal modification of eukaryotic mRNA, accounting for over 80% of all RNA base methylations in various species [4]. RNA m6A methylation is a dynamically reversible modification within the cell that is regulated by methyltransferases, demethylases, and m6A binding proteins [5,6]. The effects of m6A modification include the functional modulation of mRNA splicing, export, localization, translation, and stability by regulating RNA structure and interactions between RNA and RNA-binding proteins [7,8,9,10].
Since the 1970s, m6A modification has been known to tag not only cellular RNA but also the RNA of multiple viruses [11]. In the following decades, m6A modifications were identified in viral RNA in mammals, including simian virus 40 (SV40) [12], Rous sarcoma virus (RSV) [13], and Influenza A virus (IAV) [14]. However, the functional relevance of m6A modification has remained elusive, mainly due to the lack of efficient methods of detection and subsequent analysis. Recent studies have demonstrated the crucial roles of m6A in virus–host interactions [15,16,17]. The dynamics of m6A modifications, including the precise locations, frequency of methylation, and percentage of methylated genes, may differ in plants subjected to biotic and abiotic stress, particularly plants infected with viruses. Although m6A modification plays a crucial role in controlling the viral life cycle and reproduction in animal systems, researchers still have a limited understanding of its significance in plant viruses [17,18,19].
Plants are infected by many viruses over the course of their growth, including by double- and single-stranded DNA and RNA viruses. However, the genome of most plant viruses is RNA based. These viruses cause severe diseases in numerous crops worldwide, resulting in substantial losses to agricultural production [20]. Plant RNA viruses are classified based on their genome composition, like the single-stranded RNA positive-strand viruses from the families Potyviridae (potato virus Y [PVY]), Bromoviridae (alfalfa mosaic virus [AMV], and cucumber mosaic virus [CMV]), single-stranded RNA negative-strand viruses from the Ophioviridae family, and double-stranded RNA viruses from the Partitiviridae family [21]. The majority of plant viruses (~80%) contain single-stranded RNA genomes ranging in size from 2.5 to 10 kb, with the majority being in the range from 4 to 6 kb. During the viral infection multiple symptoms occur, the vast majority of which are host-specific [22]. The symptoms of viral infection occur as a result of complex interactions between the virus and its host plant. With advances in our understanding of RNA viruses and the development of sequencing technology, the roles of m6A modification in modulating viral infection are now being uncovered [23]. The frequency of m6A modification in tobacco (Nicotiana tabacum) exhibited a significant reduction subsequent to infection with tobacco mosaic virus (TMV) [18]. This discovery implies that the m6A modification could serve as a regulatory mechanism utilized by plants to effectively counteract viral infections. Significantly, the genomes of various single-stranded RNA plant viruses have been discovered to contain a conserved alkylation B domain sequence, which is a component of m6A demethylases [24,25]. For example, members of the family Flexiviridae, including Grapevine virus A (GVA), Blueberry scorch virus (BlScV), and Blackberry virus Y (BVY), as well as an unnamed new genus in the family Potyviridae, contain ALKB-like domains. Sequence analysis revealed that the ALKB domain may be involved in the repair of methylated RNA damage and plays an important role in clearing the viral genome of harmful RNA and maintaining the stability of viral RNA [26]. These findings confirm that some plant viruses have developed responses to this mechanism in the host, and that m6A modification may be a technique used by plants to fine-tune their responses to viral infection.
The structural diversity and functional characteristics of RNA genomes in most plant viruses pose challenges for their comprehensive characterization using conventional molecular biology methodologies [27]. Recent developments in high-throughput sequencing methods for m6A have facilitated functional research on this RNA modification. Two major methods are currently used to identify m6A modifications.
The first method is antibody-dependent m6A sequencing. (i) m6A antibody affinity enrichment combined with high-throughput sequencing (methylated RNA immunoprecipitation followed by sequencing [MeRIP-seq] or m6A-seq) was the first high-throughput sequencing technique developed using m6A antibodies. MeRIP-seq/m6A-seq is simple to perform, and all reagents have been commercialized; thus, it has always been the first choice for m6A sequencing [28,29]. (ii) In m6A individual-nucleotide-resolution cross-linking and immunoprecipitation (m6A-CLIP/miCLIP), the two methods cannot accurately locate m6A in multiple adjacent adenines, and the analysis of clustered m6A distribution is difficult [30,31]. (iii) An upgraded MeRIP-seq/m6A-seq method (m6A-seq2): performs, all m6A-IPs in a single tube, which can lower technical variability, starting material requirements, and library preparation costs [32].
The second method is antibody-independent m6A sequencing, including (i) m6A selective chemical labeling using the m6A demethylase Fat mass and obesity-associated protein (FTO) (m6A-SEAL-seq), in which the amount of initial RNA required for m6A-SEAL-seq is low, and there is almost no sequence selectivity. The disadvantages of this method are that it involves many operations and takes a long time [33]. (ii) In selective allyl chemical labeling and sequencing (m6A-SAC-seq), the reaction is based on an enzyme and may therefore have a sequence preference [34]. (iii) Glyoxal and nitrite-mediated deamination of unmethylated adenosine and sequencing (GLORI-seq) enables efficient and unbiased detection of single base m6A sites and absolute quantification of m6A modification level [35].
The rapid development of these sequencing technologies has advanced the study of plant–virus interactions. However, the molecular functions of this modification, the dynamics of m6A in plant–virus interactions, and the relationship between the expression levels of important disease resistance pathway–related genes in the host and the m6A modification regions on gene bodies in the host are all still unknown. Furthermore, plants have evolved sophisticated systems for detecting and battling viruses after a plant has been infected by a virus, including protein degradation, RNA silencing, immune receptor signaling, and hormone-mediated defense pathways. The two primary examples of plant defense systems are pathogen-associated molecular patterns (PAMP)-triggered immunity (PTI) and effector-triggered immunity (ETI). It is still unknown whether the m6A level of the viral genome is affected as well as whether some of the immune mechanisms ([PTI] and [ETI]) of the plant itself change. In this review, we focus on recent findings on the functions of N6-methyladenosine modification in plant–RNA virus interactions. We hope that this review serves as a reference for future in-depth studies of the roles and mechanisms of m6A in regulating viral infection.

2. Molecular Mechanism of m6A Modification

The deposition of m6A is achieved by a multicomponent methyltransferase complex [36]. The deposition of the m6A modification is regulated by three types of protein, commonly referred to as “writer” (m6A methyltransferase), “eraser” (m6A demethylase), and “reader” (m6A binding) proteins. Writers and erasers perform the reversible deposition and removal of this modification, respectively [37]. The first reports of m6A in plant mRNAs date back to 1979, when it was first discovered in wheat (Triticum aestivum) and maize (Zea mays) [38,39]. Shortly after the discovery of m6A in plant mRNAs, scientists identified the RRACH sequence motif (where R = G/A, H = A/C/U, with the bold letter representing the m6A-modified adenosine) [17,40]. However, despite this initial interest, research in plant m6A decreased until it was rediscovered in Arabidopsis (Arabidopsis thaliana) in 2008. In this study, the functional importance of the mRNA adenosine methylase A gene (MTA, an ortholog of human Methyltransferase 3 [METTL3]) was demonstrated through loss-of-function experiments, where disruption of the gene resulted in the death of the plant embryo [41]. Since then, Several additional m6A methyltransferases have been identified in plants, including MTB (homolog of human METTL14) [40], VIRILIZER (VIR, homolog of human KIAA1429) [42], FKBP12 Interacting Protein 37 (FIP37, homolog of human WT1-associated protein [WTAP]) [43], HAKAI [41,44], FIONA1 (FIO1, ortholog of human METTL16) [45], FLOWERING LOCUS PA (FPA, homolog of human RNA Binding Motif Protein 15 [RBM15, RBM15B]) [46], and HAKAI Interacting Zinc finger protein 1 and 2 (HIZ1 and HIZ2, homologs of human ZC3H13) [47]. Other such proteins remain to be discovered. The continuous discovery of new m6A-related proteins has driven ongoing research in this field.
In contrast to writers and readers, our knowledge about eraser proteins is limited. The alkylation B homolog (ALKBH) protein, a member of the α-ketoglutarate (αKG) and Fe (II) dioxygenase superfamily, removes alkyl and methyl groups from DNA and has been proposed to function as an RNA demethylase [29,48,49]. The functions of only a few eraser proteins in plants have been determined, and 13 Arabidopsis ALKBH family members have been identified by bioinformatics analysis [50,51]. The demethylase activities of ALKBH9B and ALKBH10B have been shown in Arabidopsis, demonstrating the functions of ALKBH9B, ALKBH10B, and ALKBH6. ALKBH10B is an mRNA m6A eraser that influences flowering, and ALKBH6 functions in seed germination, seedling growth, and the survival of Arabidopsis under abiotic stress [52,53].
Finally, several proteins that recognize the m6A modification have been identified, including reader proteins from the YTH family, named after the YT521-B homology domain they contain [28,54,55]. Plants have thirteen YTH identified family proteins, 11 of which have been designated as Evolutionarily Conserved C-Terminal Region 1–11 (ECT 1–11) and, as a predominant isoform of the polyadenylation factor CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR30 (CPSF30), CPSF30-L consists of CPSF30-S and an m6A-binding YTH domain; it was identified as a novel m6A reader in Arabidopsis. CPSF30-L is the homolog of YTHDC1; it is located in the nucleus and is involved in alternative polyadenylation (APA) regulation [56,57,58]. These studies revealed an additional function for m6A in RNA metabolism. An overview of the linked machinery and molecular activities of m6A is shown in Figure 1 [59,60].

3. Regulation of m6A Methylation in Plant RNA Viruses

A growing number of studies have shown that m6A and its related proteins play a key role in the viral infection process, and their regulatory role is summarized in Table 1 according to the different virus species. The RNAs of the plant viruses AMV and CMV contain m6A methylation. Analysis of the effect of the demethylation activity of Arabidopsis ALKBH9B(AtALKBH9B) on the infectivity of AMV showed that this protein affects the infectivity of AMV, but not CMV. The suppression of AtALKBH9B function increased the relative abundance of m6A over the AMV genome, impairing the systemic invasion of the plant while not having any effect on CMV infection [19]. The differences in the effects of AtALKBH9B on these two viruses might be related to the ability of AtALKBH9B to interact with viral coat proteins (CPs). Characterization of viral proteins is crucial for a better understanding of these virus–plant interactions as well as the characterization of host components involved in the infectious process. As already described for various plant viruses, coding regions of viral genomes, regulatory elements, non-coding sequences, or silent mutations may be involved in the induction of viral symptoms [61,62,63]. Indeed, a study to dissect the functional activity of AtALKBH9B in AMV infection indicated that amino acid residues between positions 427 and 467 were critical for the in vitro binding of AtALKBH9B to AMV RNA. The AtALKBH9B amino acid sequence contains intrinsically disordered regions located at its N-terminal region delimiting the internal AlkB-like domain and at the C-terminal region. An RNA-binding domain containing an RGxxxRGG (where R = G/A) motif that overlaps with the C-terminal intrinsically disordered region was identified in AtALKBH9B [64]. Bimolecular fluorescence complementation analysis revealed that residues located between positions 387 and 427 in AtALKBH9B interacted with AMV CP and were likely critical for modulating viral infection. Deleting either the 20 N-terminal residues or the 40 C-terminal residues in this protein impeded the accumulation of short interfering RNA (siRNA) bodies in the plant. This mechanism may represent a component of a previously unknown antiviral system because genetic depletion of a plant m6A demethylase negatively affected AMV accumulation and movement. Thus, AtALKBH9B affects the ability of AMV to infect the plant [65]. These findings suggest that m6A demethylase activity (AtALKBH9B) plays a role in AMV infection in plants. Further research is needed to systematically explain the molecular mechanism of m6A regulation of host and viral RNA during AMV infection.
AMV and CMV belong to the Bromoviridae family, but AtALKBH9B does not interact with the CP of CMV [66]. However, AtALKBH9B interacts with the CP of prunus necrotic ringspot virus (PNRSV), which is functionally and phylogenetically closely related to AMV [67,68]. However, since Arabidopsis is not a host of PNRSV, the infectivity of the virus cannot be tested in plants lacking ALKBH9B function, although AtALKBH9B may regulate the life cycles of other Bromoviridae family viruses. Since m6A plays different roles in different types of viral infection in plants, it will be important to study the roles of m6A in different viruses and hosts in the future.
Table 1. Roles of m6A in different viral infections.
Table 1. Roles of m6A in different viral infections.
Virus NameVirus ClassificationMechanismsReference
AMVBromoviridae I familyAtALKBH9B correlates with the ability to interact with AMV coat proteins.[19,65,66]
PNRSVBromoviridae I familyAtALKBH9B was found to interact with the CP of PNRSV (a functionally and phylogenetically closely related AMV).[67]
PVYPotyviridae familyPVY in Nicotiana benthamiana reduces the level of m6A methylation.[26]
PPVPotyviridae familyOverexpression of NbMETTL1 and NbMETTL2 caused a decrease in PPV accumulation.[26]
ENMVPotyviridae familyThe P1 of ENMV contains AlkB domains.[69]
WYMVPotyviridae familyTaMTB binds to the NIb of WYMV and thus promotes viral infection.[70,71]
BlVYPotyviridae familyBIVY has an AlkB domain of RNA demethylase activity.[24,69]
PepMVFlexiviridae familyRdRp encoded by PepMV could interact with SlHAKAI and promote its protein degradation.[72]
TMVVirgaviridae familyThe global m6A level was reduced under TMV infection, probably associated with decreased m6A methyltransferase and increased demethylase expression.[18]
CGMMVVirgaviridae familyClALKBH4B has a significant induction effect in the early response of resistant watermelon to CGMMV.[73]
RBSDVReoviridae familyThe m6A methylation is mainly associated with genes that are not actively expressed in virus-infected rice plants.[74,75]
RSVPhenuiviridae family[75]
Plum pox virus (PPV), PVY, and endive necrotic mosaic virus (ENMV) belong to the Potyvirus genus. Infection with PPV or PVY reduced the level of m6A methylation in Nicotiana benthamiana. NbALKB1 and NbALKB2 were amplified by Yue et al., who extracted them from cDNA samples obtained from N. benthamiana plants [26]. The authors reasoned that overexpressing these newly identified N. benthamiana ALKBH9B homologs would affect the systemic movement of PPV. However, no significant variations in PPV accumulation were observed in local (6 days post infection [dpi]) or upper non-inoculated (14 dpi) leaf samples collected from treated and control plants, as determined by immunoblotting with PPV CP-specific antiserum. However, this assay may lack the necessary sensitivity, or endogenous levels of these AlkB homologs may already have been sufficient to reach a PPV fitness maximum. Notably, the authors determined that the P1 region of ENMV contains AlkB domains and identified an additional virus from a putative new species within Potyvirus containing these domains [69]. A polyprotein leader of blackberry virus Y (BlVY), an unusual Potyvirid from the Brambyvirus genus, was found to contain a viral AlkB domain exhibiting RNA demethylase activity [24,76]. Phylogenic analysis revealed that ENMV domains share a common origin, while BlVY AlkB belongs to a divergent branch. These results show that two Potyviruses and a Brambyvirus possess the AlkB genes, multiple independent gene acquisition events have contributed to the evolution of Potyvirid AlkB, and RNA methylation likely plays a significant role in driving the evolution of Potyvirus. Further research is needed to fully understand the relationship between RNA methylation and Potyviruses. Overexpression of the ALKBH9B homolog in PPV-infected plants did not affect the systemic movement of the virus [26]. Overexpression of NbMETTL1 and NbMETTL2 (related to human METTL16 and Arabidopsis FIONA1) caused a decrease in PPV accumulation, indicating that METTL homologs participate in plant antiviral responses [77]. Collectively, these studies demonstrate that demethylase of m6A is a common modification in different plants and suggest that m6A modification plays essential roles in different plant–RNA virus interactions.
A recent study demonstrated that overexpressing the tomato (Solanum lycopersicum) m6A writer gene SlHAKAI negatively regulated pepino mosaic virus (PepMV) infection and inhibited viral RNA and protein accumulation by affecting viral m6A levels in tomato plants. On the contrary, there was a direct interaction observed between SlHAKAI and the RNA-dependent RNA polymerase (RdRp) encoded by PepMV, resulting in a decrease in the accumulation of SlHAKAI. Additionally, it has been found that PepMV RdRp exploits the autophagy pathway by directly interacting with SlBeclin1 to facilitate the autophagic degradation of SlHAKAI [72]. These findings indicate that a viral protein has the ability to exploit an autophagy factor for compromising the m6A-mediated antiviral response, which represents a novel strategy employed during the ongoing competition between plants and viruses.

4. RNA Viruses Affect m6A Methylation

DNA methylation has little effect on RNA viruses due to the absence of DNA during their replication cycle. However, RNA-based m6A has a demonstrated ability to control cytoplasmic-replicating viruses, pointing to a new layer of the defense mechanism that promotes viral infection [78]. After the virus enters the host cell, it sheds its coat to release its genomic RNA, which is interpreted by transfer RNAs (tRNAs) and the host ribosome using viral RNA as the template. The codon sequences stored in the viral RNA are converted into amino acid sequences, and the products related to viral genome replication are translated. The proteases of the host plant change in response to viral infection, and several methyltransferases may interact with viral proteins and promote viral infection. During wheat yellow mosaic virus (WYMV) infection, resistant and susceptible wheat varieties exhibit a significant variation in their m6A modification patterns. Transcriptome-wide m6A profiling of WYMV-infected resistant and susceptible wheat varieties revealed that differential m6A modifications may disrupt host–pathogen interaction pathways by regulating the expression of related genes [74,75]. The genes investigated in these studies are closely associated with plant defense mechanisms and resilience against pathogens. As a result, they have been considered as potential genes for investigating the strategies employed by wheat to resist viral infections and for understanding the mechanisms through which viruses effectively invade wheat plants. Translocation of wheat m6A methyltransferase B (TaMTB) into cytoplasmic aggregates is facilitated by its interaction with the NIb protein of WYMV. This interaction leads to an increase in the m6A levels of WYMV genomic RNA1 and stabilization of viral RNA, thereby facilitating viral infection. TaMTB may function as an m6A methyltransferase that relocates to cytoplasmic punctate structures upon binding with WYMV NIb protein, suggesting that m6A methyltransferases play a role in viral life cycle and regulation of viral involvement in host antiviral innate immunity [79]. Further experimental investigations are required to validate the regulatory impact of m6A RNA modifications on the expression of these candidate genes during plant defense against viral infection.
Viral infection also affects the m6A levels of endogenous host RNA. One study reported that the m6A level decreased in tobacco following TMV infection [18]. In contrast, a study of high-quality m6A methylomes of rice (Oryza sativa) plants infected with rice stripe virus (RSV) or rice black-stripe dwarf virus (RBSDV) revealed increased levels of m6A in rice RNA following RSV or RBSDV infection; this m6A methylation was mainly associated with genes that are not actively expressed in virus-infected rice plants [74]. These findings suggest that the regulation of plant m6A by viral invasion is complex. The overall plant m6A level is altered by RNA viruses of the genera Tobamovirus, Bymovirus, Tenuivirus, and Fijivirus [79]. m6A modifications in various models were observed on the same gene, possibly reflecting different disease resistance models after two viral infections. For instance, in RBSDV- and RSV-infected samples, the writer genes OsMTA3 and OsMTA4 underwent m6A methylation. The eraser genes OsALKBH10B and OsALKBH9B experienced m6A modification only in RSV-infected samples, while no eraser genes showed m6A methylation in RBSDV-infected samples. Regarding reader genes, RBSDV-infection led to m6A methylation of OsYTH01, OsYTH10, OsYTH11, and OsYTH12, whereas RSV-infection resulted in m6A methylation of OsYTH05 and OsYTH08. Several antiviral pathway-related genes, such as genes involved in RNA silencing, resistance, and fundamental antiviral phytohormone metabolism, were also m6A-methylated. The level of m6A methylation is tightly associated with the relative expression level of a gene. These observations highlight the importance of m6A modification in plant–virus interactions, especially in regulating the expression of genes associated with key pathways.
The tobamovirus cucumber green mottle mosaic virus (CGMMV) has been considered to be the major global plant virus in cucurbit plants. The induction of fruit decay is among the most severe symptoms and is responsible for significant production losses [73]. To discover the molecular mechanism involved in the induction fruit decay He et al. analyzed the m6A methylation spectrum in the response of watermelon (Citrullus lanatus) to CGMMV infection, using Gene Ontology analysis combined with a transcriptome deep sequencing (RNA-seq) approach, and analysis of the response patterns and putative functions of differentially expressed and m6A-modified genes in the transcriptome of CGMMV-infected watermelon leaves. Research shows that the global m6A level in resistant watermelon clearly decreased after CGMMV infection. Both the m6A methylation and transcript levels of 59 modified genes significantly changed in response to CGMMV infection; some of these genes are involved in plant immunity. The authors proposed a preliminary hypothesis to explain the mechanism of the resistance of watermelon to viral infection via m6A modification: the m6A demethylase gene ClALKBH4B is significantly induced as an early response to CGMMV in resistant watermelon, and the decreased expression of ClALKBH4B results in the methylation of numerous target genes, leading to their downregulation. The m6A methylation of transcripts is generally negatively correlated with transcript levels. Therefore, the expression of various downstream defense response factors involved in virus-induced gene silencing, transcription factor genes, and genes involved in plant carbohydrate allocation and signaling is induced (as revealed by RNA-seq) and a series of plant immune responses are activated during the early stage of CGMMV infection. Whether changes in the m6A modification of these genes affects viral replication deserves further study.

5. Conclusions and Perspectives

m6A modification is dynamic, reversible, and widely involved in the modification of host and viral RNA; it modulates complex regulatory mechanisms and diverse activities. m6A plays different roles in different viruses, different host cells, and even at different times. m6A can directly modify viral RNA, thereby affecting viral gene expression or host immune system recognition. This modification can also indirectly regulate viral infection by regulating expression of host genes, such as genes in the host innate immune pathway, cell metabolic pathways, and other related genes. Although many studies have shown that m6A modification has an important regulatory role in the viral life cycle, its regulatory mechanism is not yet clear. Therefore, m6A modification in the context of plant–virus interactions remains largely unexplored. There is a need for a better understanding of how m6A modification affects the interplay between plant hosts and viral pathogens.
To date, m6A methyltransferase and m6A demethylase have been shown to function in RNA virus–plant host interactions to affect the host or virus, but there has been no breakthrough in identifying m6A binding proteins. In fact, the role of methylation depends on the m6A reader protein [55]. m6A modification is also involved in the interaction between plants and pathogenic fungi. Guo et al. [80] discovered the role of an m6A binding protein (MhYTP2 from Chinese crab apple [Malus hupehensis]) in plant–microbe interactions. By accelerating the degradation of the bound mRNAs of MdMLO19 and MdMLO19-X1 and increasing the translation efficiency of antioxidant genes, MhYTP2, a homolog of EVOLUTIONARILY CONSERVED C-TERMINAL REGION 2 (ECT2), enhanced apple resistance to powdery mildew. Magnaporthe oryzae RNA’s m6A alteration was the subject of another investigation [81]. The functional significance of the m6A alteration for M. oryzae infection was highlighted by the fact that MTA1, which is involved in m6A modification, is deficient. This results in decreased appressorial penetration, invasive development of M. oryzae, and highly disrupted autophagy in the mutant. Thus, m6A binding proteins may also influence pathogenic bacteria. In addition, the roles of m6A binding proteins in different viruses should be studied.
To fulfill the constantly increasing need for food and feed, innovative agricultural practices are required [82]. In two crops, overexpressing m6A demethylase genes increased yield by almost 50%, according to a recent ground-breaking study [83]. New approaches to virus control and epigenetic reprogramming of agricultural attributes might be sparked by improvements in the customized manipulation of RNA methylation by plant genome engineering or viral vector delivery. Indeed, whereas recent studies have demonstrated that changes in m6A modification in viral or host RNA can regulate viral infection, the specific regulatory mechanism has not yet been deeply studied. Future research may need to comprehensively consider various factors (e.g., cell type, viral strain and infection time) and use optimal sequencing technologies to systematically analyze the roles and specific mechanisms of virus or host m6A in the viral replication cycle to provide a new theoretical basis for antiviral research.

Author Contributions

M.H. and Z.L. collected the documents and wrote the manuscript. X.X. conceived and developed the idea of this review and designed the overall concept X.X. revised the manuscript. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the Guizhou Provincial Key Technology R&D Program ([2022]091), the Open Research Fund of State Key Laboratory for Biology of Plant Diseases and Insect Pests (SKLOF202309), and the China Postdoctoral Science Foundation (2022MD713740).

Acknowledgments

We would like to thank Entaj Tarafder, Fen Wang, and Wende Liu for revising this manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Li, X.; Xiong, X.; Yi, C. Epitranscriptome sequencing technologies: Decoding RNA modifications. Nat. Methods 2017, 14, 23–31. [Google Scholar] [CrossRef] [PubMed]
  2. Ping, X.-L.; Sun, B.-F.; Wang, L.; Xiao, W.; Yang, X.; Wang, W.-J.; Adhikari, S.; Shi, Y.; Lv, Y.; Chen, Y.-S. Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res. 2014, 24, 177–189. [Google Scholar] [CrossRef] [PubMed]
  3. He, P.C.; He, C. m6A RNA methylation: From mechanisms to therapeutic potential. EMBO J. 2021, 40, e105977. [Google Scholar] [CrossRef] [PubMed]
  4. Yue, Y.; Liu, J.; He, C. RNA N6-methyladenosine methylation in post-transcriptional gene expression regulation. Genes Dev. 2015, 29, 1343–1355. [Google Scholar] [CrossRef]
  5. Fu, Y.; Dominissini, D.; Rechavi, G.; He, C. Gene expression regulation mediated through reversible m6A RNA methylation. Nat. Rev. Genet. 2014, 15, 293–306. [Google Scholar] [CrossRef]
  6. Meyer, K.D.; Jaffrey, S.R. The dynamic epitranscriptome: N6-methyladenosine and gene expression control. Nat. Rev. Mol. Cell Biol. 2014, 15, 313–326. [Google Scholar] [CrossRef]
  7. Wang, P.; Doxtader, K.A.; Nam, Y. Structural basis for cooperative function of Mettl3 and Mettl14 methyltransferases. Mol. Cell 2016, 63, 306–317. [Google Scholar] [CrossRef]
  8. Fu, Y.; Jia, G.; Pang, X.; Wang, R.N.; Wang, X.; Li, C.J.; Smemo, S.; Dai, Q.; Bailey, K.A.; Nobrega, M.A. FTO-mediated formation of N6-hydroxymethyladenosine and N 6-formyladenosine in mammalian RNA. Nat. Commun. 2013, 4, 1798. [Google Scholar] [CrossRef]
  9. Wang, X.; Zhao, B.S.; Roundtree, I.A.; Lu, Z.; Han, D.; Ma, H.; Weng, X.; Chen, K.; Shi, H.; He, C. N6-methyladenosine modulates messenger RNA translation efficiency. Cell 2015, 161, 1388–1399. [Google Scholar] [CrossRef]
  10. Vu, L.P.; Pickering, B.F.; Cheng, Y.; Zaccara, S.; Nguyen, D.; Minuesa, G.; Chou, T.; Chow, A.; Saletore, Y.; MacKay, M. The N6-methyladenosine (m6A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells. Nat. Med. 2017, 23, 1369–1376. [Google Scholar] [CrossRef]
  11. Desrosiers, R.; Friderici, K.; Rottman, F. Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. Proc. Natl. Acad. Sci. USA 1974, 71, 3971–3975. [Google Scholar] [CrossRef] [PubMed]
  12. Canaani, D.; Kahana, C.; Lavi, S.; Groner, Y. Identification and mapping of N6-methyladenosine containing sequences in simian virus 40 RNA. Nucleic Acids Res. 1979, 6, 2879–2899. [Google Scholar] [CrossRef] [PubMed]
  13. Beemon, K.; Keith, J. Localization of N6-methyladenosine in the Rous sarcoma virus genome. J. Mol. Biol. 1977, 113, 165–179. [Google Scholar] [CrossRef] [PubMed]
  14. Narayan, P.; Ayers, D.F.; Rottman, F.M.; Maroney, P.A.; Nilsen, T.W. Unequal distribution of N 6-methyladenosine in influenza virus mRNAs. Mol. Cell. Biol. 1987, 7, 1572–1575. [Google Scholar]
  15. Dang, W.; Xie, Y.; Cao, P.; Xin, S.; Wang, J.; Li, S.; Li, Y.; Lu, J. N6-methyladenosine and viral infection. Front. Microbiol. 2019, 10, 417. [Google Scholar] [CrossRef]
  16. Williams, G.D.; Gokhale, N.S.; Horner, S.M. Regulation of viral infection by the RNA modification N6-methyladenosine. Annu. Rev. Virol. 2019, 6, 235–253. [Google Scholar] [CrossRef]
  17. Arribas-Hernández, L.; Brodersen, P. Occurrence and functions of m6A and other covalent modifications in plant mRNA. Plant Physiol. 2020, 182, 79–96. [Google Scholar] [CrossRef]
  18. Li, Z.; Shi, J.; Yu, L.; Zhao, X.; Ran, L.; Hu, D.; Song, B. N6-methyl-adenosine level in Nicotiana tabacum is associated with tobacco mosaic virus. Virol. J. 2018, 15, 87. [Google Scholar] [CrossRef]
  19. Martínez-Pérez, M.; Aparicio, F.; López-Gresa, M.P.; Bellés, J.M.; Sánchez-Navarro, J.A.; Pallás, V. Arabidopsis m6A demethylase activity modulates viral infection of a plant virus and the m6A abundance in its genomic RNAs. Proc. Natl. Acad. Sci. USA 2017, 114, 10755–10760. [Google Scholar] [CrossRef]
  20. Roossinck, M.J. Plant RNA virus evolution. Curr. Opin. Microbiol. 2003, 6, 406–409. [Google Scholar] [CrossRef]
  21. Laliberté, J.-F.; Sanfaçon, H. Cellular remodeling during plant virus infection. Annu. Rev. Phytopathol. 2010, 48, 69–91. [Google Scholar] [CrossRef] [PubMed]
  22. Zhao, J.; Zhang, X.; Hong, Y.; Liu, Y. Chloroplast in plant-virus interaction. Front. Microbiol. 2016, 7, 1565. [Google Scholar] [CrossRef] [PubMed]
  23. Yue, J.; Wei, Y.; Zhao, M. The reversible methylation of m6A is involved in plant virus infection. Biology 2022, 11, 271. [Google Scholar] [CrossRef] [PubMed]
  24. van den Born, E.; Omelchenko, M.V.; Bekkelund, A.; Leihne, V.; Koonin, E.V.; Dolja, V.V.; Falnes, P.Ø. Viral AlkB proteins repair RNA damage by oxidative demethylation. Nucleic Acids Res. 2008, 36, 5451–5461. [Google Scholar] [CrossRef]
  25. Bratlie, M.S.; Drabløs, F. Bioinformatic mapping of AlkB homology domains in viruses. BMC Genom. 2005, 6, 1. [Google Scholar] [CrossRef]
  26. Yue, J.; Wei, Y.; Sun, Z.; Chen, Y.; Wei, X.; Wang, H.; Pasin, F.; Zhao, M. AlkB RNA demethylase homologues and N6-methyladenosine are involved in Potyvirus infection. Mol. Plant Pathol. 2022, 23, 1555–1564. [Google Scholar] [CrossRef]
  27. Zanardo, L.G.; de Souza, G.B.; Alves, M.S. Transcriptomics of plant–virus interactions: A review. Theor. Exp. Plant Physiol. 2019, 31, 103–125. [Google Scholar] [CrossRef]
  28. Dominissini, D.; Moshitch-Moshkovitz, S.; Schwartz, S.; Salmon-Divon, M.; Ungar, L.; Osenberg, S.; Cesarkas, K.; Jacob-Hirsch, J.; Amariglio, N.; Kupiec, M. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 2012, 485, 201–206. [Google Scholar] [CrossRef]
  29. Meyer, K.D.; Saletore, Y.; Zumbo, P.; Elemento, O.; Mason, C.E.; Jaffrey, S.R. Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell 2012, 149, 1635–1646. [Google Scholar] [CrossRef]
  30. Ke, S.; Alemu, E.A.; Mertens, C.; Gantman, E.C.; Fak, J.J.; Mele, A.; Haripal, B.; Zucker-Scharff, I.; Moore, M.J.; Park, C.Y. A majority of m6A residues are in the last exons, allowing the potential for 3′ UTR regulation. Genes Dev. 2015, 29, 2037–2053. [Google Scholar] [CrossRef]
  31. Linder, B.; Grozhik, A.V.; Olarerin-George, A.O.; Meydan, C.; Mason, C.E.; Jaffrey, S.R. Single-nucleotide-resolution mapping of m6A and m6Am throughout the transcriptome. Nat. Methods 2015, 12, 767–772. [Google Scholar] [CrossRef] [PubMed]
  32. Dierks, D.; Garcia-Campos, M.A.; Uzonyi, A.; Safra, M.; Edelheit, S.; Rossi, A.; Sideri, T.; Varier, R.A.; Brandis, A.; Stelzer, Y. Multiplexed profiling facilitates robust m6A quantification at site, gene and sample resolution. Nat. Methods 2021, 18, 1060–1067. [Google Scholar] [CrossRef] [PubMed]
  33. Wang, Y.; Xiao, Y.; Dong, S.; Yu, Q.; Jia, G. Antibody-free enzyme-assisted chemical approach for detection of N 6-methyladenosine. Nat. Chem. Biol. 2020, 16, 896–903. [Google Scholar] [CrossRef] [PubMed]
  34. Hu, L.; Liu, S.; Peng, Y.; Ge, R.; Su, R.; Senevirathne, C.; Harada, B.T.; Dai, Q.; Wei, J.; Zhang, L. m6A RNA modifications are measured at single-base resolution across the mammalian transcriptome. Nat. Biotechnol. 2022, 40, 1210–1219. [Google Scholar] [CrossRef] [PubMed]
  35. Liu, C.; Sun, H.; Yi, Y.; Shen, W.; Li, K.; Xiao, Y.; Li, F.; Li, Y.; Hou, Y.; Lu, B. Absolute quantification of single-base m6A methylation in the mammalian transcriptome using GLORI. Nat. Biotechnol. 2023, 41, 355–366. [Google Scholar] [CrossRef]
  36. Bokar, J.A.; Rath-Shambaugh, M.E.; Ludwiczak, R.; Narayan, P.; Rottman, F. Characterization and partial purification of mRNA N6-adenosine methyltransferase from HeLa cell nuclei. Internal mRNA methylation requires a multisubunit complex. J. Biol. Chem. 1994, 269, 17697–17704. [Google Scholar] [CrossRef]
  37. Yang, C.; Hu, Y.; Zhou, B.; Bao, Y.; Li, Z.; Gong, C.; Yang, H.; Wang, S.; Xiao, Y. The role of m6A modification in physiology and disease. Cell Death Dis. 2020, 11, 960. [Google Scholar] [CrossRef]
  38. Nichols, J. N6-methyladenosine in maize poly (A)-containing RNA. Plant Sci. Lett. 1979, 15, 357–361. [Google Scholar] [CrossRef]
  39. Kennedy, T.; Lane, B. Wheat embryo ribonucleates. XIII. Methyl-substituted nucleoside constituents and 5′-terminal dinucleotide sequences in bulk poly (A)-rich RNA from imbibing wheat embryos. Can. J. Biochem. 1979, 57, 927–931. [Google Scholar] [CrossRef]
  40. Nichols, J.; Welder, L. Nucleotides adjacent to N6-methyladenosine in maize poly (A)-containing RNA. Plant Sci. Lett. 1981, 21, 75–81. [Google Scholar] [CrossRef]
  41. Zhong, S.; Li, H.; Bodi, Z.; Button, J.; Vespa, L.; Herzog, M.; Fray, R.G. MTA is an Arabidopsis messenger RNA adenosine methylase and interacts with a homolog of a sex-specific splicing factor. Plant Cell 2008, 20, 1278–1288. [Google Scholar] [CrossRef]
  42. Růžička, K.; Zhang, M.; Campilho, A.; Bodi, Z.; Kashif, M.; Saleh, M.; Eeckhout, D.; El-Showk, S.; Li, H.; Zhong, S. Identification of factors required for m6A mRNA methylation in Arabidopsis reveals a role for the conserved E3 ubiquitin ligase HAKAI. New Phytol. 2017, 215, 157–172. [Google Scholar] [CrossRef]
  43. Vespa, L.; Vachon, G.; Berger, F.; Perazza, D.; Faure, J.-D.; Herzog, M. The immunophilin-interacting protein AtFIP37 from Arabidopsis is essential for plant development and is involved in trichome endoreduplication. Plant Physiol. 2004, 134, 1283–1292. [Google Scholar] [CrossRef] [PubMed]
  44. Wang, Y.; Zhang, L.; Ren, H.; Ma, L.; Guo, J.; Mao, D.; Lu, Z.; Lu, L.; Yan, D. Role of Hakai in m6A modification pathway in Drosophila. Nat. Commun. 2021, 12, 2159. [Google Scholar] [CrossRef] [PubMed]
  45. Xu, T.; Wu, X.; Wong, C.E.; Fan, S.; Zhang, Y.; Zhang, S.; Liang, Z.; Yu, H.; Shen, L. FIONA1-Mediated m6A Modification Regulates the Floral Transition in Arabidopsis. Adv. Sci. 2022, 9, 2103628. [Google Scholar] [CrossRef]
  46. Parker, M.T.; Knop, K.; Zacharaki, V.; Sherwood, A.V.; Tome, D.; Yu, X.; Martin, P.G.; Beynon, J.; Michaels, S.D.; Barton, G.J. Widespread premature transcription termination of Arabidopsis thaliana NLR genes by the spen protein FPA. Elife 2021, 10, e65537. [Google Scholar] [CrossRef] [PubMed]
  47. Zhang, M.; Bodi, Z.; Mackinnon, K.; Zhong, S.; Archer, N.; Mongan, N.P.; Simpson, G.G.; Fray, R.G. Two zinc finger proteins with functions in m6A writing interact with HAKAI. Nat. Commun. 2022, 13, 1127. [Google Scholar] [CrossRef]
  48. Alemu, E.A.; He, C.; Klungland, A. ALKBHs-facilitated RNA modifications and de-modifications. DNA Repair 2016, 44, 87–91. [Google Scholar] [CrossRef]
  49. Fedeles, B.I.; Singh, V.; Delaney, J.C.; Li, D.; Essigmann, J.M. The AlkB family of Fe (II)/α-ketoglutarate-dependent dioxygenases: Repairing nucleic acid alkylation damage and beyond. J. Biol. Chem. 2015, 290, 20734–20742. [Google Scholar] [CrossRef]
  50. Marcinkowski, M.; Pilžys, T.; Garbicz, D.; Steciuk, J.; Zugaj, D.; Mielecki, D.; Sarnowski, T.J.; Grzesiuk, E. Human and Arabidopsis alpha-ketoglutarate-dependent dioxygenase homolog proteins—New players in important regulatory processes. IUBMB Life 2020, 72, 1126–1144. [Google Scholar] [CrossRef]
  51. Mielecki, D.; Zugaj, D.Ł.; Muszewska, A.; Piwowarski, J.; Chojnacka, A.; Mielecki, M.; Nieminuszczy, J.; Grynberg, M.; Grzesiuk, E. Novel AlkB dioxygenases—Alternative models for in silico and in vivo studies. PLoS ONE 2012, 7, e30588. [Google Scholar] [CrossRef] [PubMed]
  52. Duan, H.-C.; Wei, L.-H.; Zhang, C.; Wang, Y.; Chen, L.; Lu, Z.; Chen, P.R.; He, C.; Jia, G. ALKBH10B is an RNA N6-methyladenosine demethylase affecting Arabidopsis floral transition. Plant Cell 2017, 29, 2995–3011. [Google Scholar] [CrossRef] [PubMed]
  53. Huong, T.T.; Ngoc, L.N.T.; Kang, H. Functional characterization of a putative RNA demethylase ALKBH6 in Arabidopsis growth and abiotic stress responses. Int. J. Mol. Sci. 2020, 21, 6707. [Google Scholar] [CrossRef] [PubMed]
  54. Patil, D.P.; Pickering, B.F.; Jaffrey, S.R. Reading m6A in the transcriptome: m6A-binding proteins. Trends Cell Biol. 2018, 28, 113–127. [Google Scholar] [CrossRef]
  55. Meyer, K.D.; Jaffrey, S.R. Rethinking m6A readers, writers, and erasers. Annu. Rev. Cell Dev. Biol. 2017, 33, 319–342. [Google Scholar] [CrossRef]
  56. Song, P.; Yang, J.; Wang, C.; Lu, Q.; Shi, L.; Tayier, S.; Jia, G. Arabidopsis N6-methyladenosine reader CPSF30-L recognizes FUE signals to control polyadenylation site choice in liquid-like nuclear bodies. Mol. Plant 2021, 14, 571–587. [Google Scholar] [CrossRef]
  57. Wei, L.-H.; Song, P.; Wang, Y.; Lu, Z.; Tang, Q.; Yu, Q.; Xiao, Y.; Zhang, X.; Duan, H.-C.; Jia, G. The m6A reader ECT2 controls trichome morphology by affecting mRNA stability in Arabidopsis. Plant Cell 2018, 30, 968–985. [Google Scholar] [CrossRef]
  58. Pontier, D.; Picart, C.; El Baidouri, M.; Roudier, F.; Xu, T.; Lahmy, S.; Llauro, C.; Azevedo, J.; Laudié, M.; Attina, A. The m6A pathway protects the transcriptome integrity by restricting RNA chimera formation in plants. Life Sci. Alliance 2019, 2, e201900393. [Google Scholar] [CrossRef]
  59. Shen, L.; Liang, Z.; Wong, C.E.; Yu, H. Messenger RNA modifications in plants. Trends Plant Sci. 2019, 24, 328–341. [Google Scholar] [CrossRef]
  60. Zhang, L.; Hanada, K.; Palukaitis, P. Mapping local and systemic symptom determinants of cucumber mosaic cucumovirus in tobacco. J. Gen. Virol. 1994, 75, 3185–3191. [Google Scholar] [CrossRef]
  61. Hirata, H.; Lu, X.; Yamaji, Y.; Kagiwada, S.; Ugaki, M.; Namba, S. A single silent substitution in the genome of Apple stem grooving virus causes symptom attenuation. J. Gen. Virol. 2003, 84, 2579–2583. [Google Scholar] [CrossRef] [PubMed]
  62. Hasiów-Jaroszewska, B.; Borodynko, N.; Jackowiak, P.; Figlerowicz, M.; Pospieszny, H. Single mutation converts mild pathotype of the Pepino mosaic virus into necrotic one. Virus Res. 2011, 159, 57–61. [Google Scholar] [CrossRef]
  63. Yue, H.; Nie, X.; Yan, Z.; Weining, S. N6-methyladenosine regulatory machinery in plants: Composition, function and evolution. Plant Biotechnol. J. 2019, 17, 1194–1208. [Google Scholar] [CrossRef] [PubMed]
  64. Thandapani, P.; O’Connor, T.R.; Bailey, T.L.; Richard, S. Defining the RGG/RG motif. Mol. Cell 2013, 50, 613–623. [Google Scholar] [CrossRef] [PubMed]
  65. Alvarado-Marchena, L.; Marquez-Molins, J.; Martinez-Perez, M.; Aparicio, F.; Pallás, V. Mapping of Functional Subdomains in the atALKBH9B m6A-Demethylase Required for Its Binding to the Viral RNA and to the Coat Protein of Alfalfa Mosaic Virus. Front. Plant Sci. 2021, 12, 701683. [Google Scholar] [CrossRef]
  66. Bujarski, J.; Gallitelli, D.; García-Arenal, F.; Pallás, V.; Palukaitis, P.; Reddy, M.K.; Wang, A.; Consortium, I.R. ICTV virus taxonomy profile: Bromoviridae. J. Gen. Virol. 2019, 100, 1206–1207. [Google Scholar] [CrossRef]
  67. Aparicio, F.; Sánchez-Navarro, J.; Olsthoorn, R.; Pallás, V.; Bol, J. Recognition of cis-acting sequences in RNA 3 of Prunus necrotic ringspot virus by the replicase of Alfalfa mosaic virus. J. Gen. Virol. 2001, 82, 947–951. [Google Scholar] [CrossRef]
  68. Sánchez-Navarro, J.; Reusken, C.; Bol, J.; Pallás, V. Replication of alfalfa mosaic virus RNA 3 with movement and coat protein genes replaced by corresponding genes of Prunus necrotic ringspot ilarvirus. J. Gen. Virol. 1997, 78, 3171–3176. [Google Scholar] [CrossRef]
  69. Desbiez, C.; Schoeny, A.; Maisonneuve, B.; Berthier, K.; Bornard, I.; Chandeysson, C.; Fabre, F.; Girardot, G.; Gognalons, P.; Lecoq, H. Molecular and biological characterization of two potyviruses infecting lettuce in southeastern France. Plant Pathol. 2017, 66, 970–979. [Google Scholar] [CrossRef]
  70. Zhang, T.-Y.; Wang, Z.-Q.; Hu, H.-C.; Chen, Z.-Q.; Liu, P.; Gao, S.-Q.; Zhang, F.; He, L.; Jin, P.; Xu, M.-Z. Transcriptome-wide N6-methyladenosine (m6A) profiling of susceptible and resistant wheat varieties reveals the involvement of variety-specific m6A modification involved in virus-host interaction pathways. Front. Microbiol. 2021, 12, 656302. [Google Scholar] [CrossRef]
  71. Zhang, T.; Liu, P.; Zhong, K.; Zhang, F.; Xu, M.; He, L.; Jin, P.; Chen, J.; Yang, J. Wheat yellow mosaic virus NIb interacting with host light induced protein (LIP) facilitates its infection through perturbing the abscisic acid pathway in wheat. Biology 2019, 8, 80. [Google Scholar] [CrossRef] [PubMed]
  72. He, H.; Ge, L.; Li, Z.; Zhou, X.; Li, F. Pepino mosaic virus antagonizes plant m6A modification by promoting the autophagic degradation of the m6A writer HAKAI. aBIOTECH 2023, 4, 83–96. [Google Scholar] [CrossRef] [PubMed]
  73. He, Y.; Li, L.; Yao, Y.; Li, Y.; Zhang, H.; Fan, M. Transcriptome-wide N6-methyladenosine (m6A) methylation in watermelon under CGMMV infection. BMC Plant Biol. 2021, 21, 516. [Google Scholar] [CrossRef] [PubMed]
  74. Tian, S.; Wu, N.; Zhang, L.; Wang, X. RNA N6-methyladenosine modification suppresses replication of rice black streaked dwarf virus and is associated with virus persistence in its insect vector. Mol. Plant Pathol. 2021, 22, 1070–1081. [Google Scholar] [CrossRef] [PubMed]
  75. Zhang, K.; Zhuang, X.; Dong, Z.; Xu, K.; Chen, X.; Liu, F.; He, Z. The dynamics of N6-methyladenine RNA modification in interactions between rice and plant viruses. Genome Biol. 2021, 22, 189. [Google Scholar] [CrossRef] [PubMed]
  76. Susaimuthu, J.; Tzanetakis, I.E.; Gergerich, R.C.; Martin, R.R. A member of a new genus in the Potyviridae infects Rubus. Virus Res. 2008, 131, 145–151. [Google Scholar] [CrossRef]
  77. Yue, J.; Lu, Y.; Sun, Z.; Guo, Y.; San León, D.; Pasin, F.; Zhao, M. Methyltransferase-like (METTL) homologues participate in Nicotiana benthamiana antiviral responses. Plant Signal. Behav. 2023, 18, 2214760. [Google Scholar] [CrossRef]
  78. Brocard, M.; Ruggieri, A.; Locker, N. m6A RNA methylation, a new hallmark in virus-host interactions. J. Gen. Virol. 2017, 98, 2207–2214. [Google Scholar] [CrossRef]
  79. Zhang, T.; Shi, C.; Hu, H.; Zhang, Z.; Wang, Z.; Chen, Z.; Feng, H.; Liu, P.; Guo, J.; Lu, Q. N6-methyladenosine RNA modification promotes viral genomic RNA stability and infection. Nat. Commun. 2022, 13, 6576. [Google Scholar] [CrossRef]
  80. Guo, T.; Liu, C.; Meng, F.; Hu, L.; Fu, X.; Yang, Z.; Wang, N.; Jiang, Q.; Zhang, X.; Ma, F. The m6A reader MhYTP2 regulates MdMLO19 mRNA stability and antioxidant genes translation efficiency conferring powdery mildew resistance in apple. Plant Biotechnol. J. 2022, 20, 511–525. [Google Scholar] [CrossRef]
  81. Ren, Z.; Tang, B.; Xing, J.; Liu, C.; Cai, X.; Hendy, A.; Kamran, M.; Liu, H.; Zheng, L.; Huang, J. MTA1-mediated RNA m6A modification regulates autophagy and is required for infection of the rice blast fungus. New Phytol. 2022, 235, 247–262. [Google Scholar] [CrossRef] [PubMed]
  82. Steinwand, M.A.; Ronald, P.C. Crop biotechnology and the future of food. Nat. Food 2020, 1, 273–283. [Google Scholar] [CrossRef]
  83. Yu, Q.; Liu, S.; Yu, L.; Xiao, Y.; Zhang, S.; Wang, X.; Xu, Y.; Yu, H.; Li, Y.; Yang, J. RNA demethylation increases the yield and biomass of rice and potato plants in field trials. Nat. Biotechnol. 2021, 39, 1581–1588. [Google Scholar] [CrossRef] [PubMed]
Ijms 24 15608 g001
Figure 1. m6A methylation pathways and related m6A methylated genes in plant-RNA virus interactions. The m6A modification is regulated by the “writers”, “erasers”, and “readers”. Writers are MTA, MTB, VIR, HAKAI, FIP37, FIONA1, FPA, and HIZ1-2, which have been reported to induce m6A RNA methylation. Among them, HAKAI interacts with RdRp encodes for PepMV, MTB binds to the NIb of WYMV promoting viral infection, and overexpression FIONA1 causes a decrease in PPV. Erasers are m6A demethylases, including ALKBH10B, SIALKBH2, ALKBH9B, and ALKBH4B. AtALKBH9B interacts with AMV and PNRSV coat protein; ClALKBH4B could induce CGMMV. Readers are proteins that bind to m6A-modified mRNAs and play corresponding roles. Proteins that have been identified as readers to date include ECT2, ECT3, ECT4, CPSF30, and MhYTP2. TMV, PVY, and RBSDV reduce or affect the level of m6A methylation. WYMV, wheat yellow mosaic virus; AMV, alfalfa mosaic virus; PNRSV, Prunus necrotic ringspot virus; CGMMV, cucumber green mottle mosaic virus; PVY, Potato virus Y; RBSDV, rice black-stripe dwarf virus; TMV, tobacco mosaic virus; PepMV, pepino mosaic virus; PPV, plum pox virus.
Figure 1. m6A methylation pathways and related m6A methylated genes in plant-RNA virus interactions. The m6A modification is regulated by the “writers”, “erasers”, and “readers”. Writers are MTA, MTB, VIR, HAKAI, FIP37, FIONA1, FPA, and HIZ1-2, which have been reported to induce m6A RNA methylation. Among them, HAKAI interacts with RdRp encodes for PepMV, MTB binds to the NIb of WYMV promoting viral infection, and overexpression FIONA1 causes a decrease in PPV. Erasers are m6A demethylases, including ALKBH10B, SIALKBH2, ALKBH9B, and ALKBH4B. AtALKBH9B interacts with AMV and PNRSV coat protein; ClALKBH4B could induce CGMMV. Readers are proteins that bind to m6A-modified mRNAs and play corresponding roles. Proteins that have been identified as readers to date include ECT2, ECT3, ECT4, CPSF30, and MhYTP2. TMV, PVY, and RBSDV reduce or affect the level of m6A methylation. WYMV, wheat yellow mosaic virus; AMV, alfalfa mosaic virus; PNRSV, Prunus necrotic ringspot virus; CGMMV, cucumber green mottle mosaic virus; PVY, Potato virus Y; RBSDV, rice black-stripe dwarf virus; TMV, tobacco mosaic virus; PepMV, pepino mosaic virus; PPV, plum pox virus.
Ijms 24 15608 g001
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

He, M.; Li, Z.; Xie, X. The Roles of N6-Methyladenosine Modification in Plant–RNA Virus Interactions. Int. J. Mol. Sci. 2023, 24, 15608. https://doi.org/10.3390/ijms242115608

AMA Style

He M, Li Z, Xie X. The Roles of N6-Methyladenosine Modification in Plant–RNA Virus Interactions. International Journal of Molecular Sciences. 2023; 24(21):15608. https://doi.org/10.3390/ijms242115608

Chicago/Turabian Style

He, Min, Zhiqiang Li, and Xin Xie. 2023. "The Roles of N6-Methyladenosine Modification in Plant–RNA Virus Interactions" International Journal of Molecular Sciences 24, no. 21: 15608. https://doi.org/10.3390/ijms242115608

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop