The expanding role of m⁶A RNA modification in plant-virus dynamics: friend, foe, or both?

Abstract

N⁶-methyladenosine (m⁶A), the most prevalent internal mRNA modification, regulates plant development and stress responses through modulating various mRNA metabolic processes and epigenetic effects. Although well studied in animals, its roles in plant–virus interactions have only recently begun to be elucidated. Multiple plant viruses carry m⁶A modifications on their RNAs, validated by MeRIP-seq, LC–MS/MS, and direct RNA sequencing. Viral RNAs acquire m⁶A through the recruitment or relocalization of host methyltransferase complexes, which is often mediated by viral proteins. Functionally, m⁶A can restrict infection by promoting viral RNA decay via YTH-domain readers and RNA surveillance pathways, or alternatively stabilize viral RNAs to enhance replication and systemic spread. In turn, viruses disrupt the functionality of host m⁶A machinery to promote infection. Moreover, viral infection reprograms host m⁶A homeostasis, altering methylation landscapes in immune and hormone pathways. These findings establish m⁶A as a dynamic epitranscriptomic switch in plant-virus interactions, with promising implications for antiviral strategies and crop improvement.

Introduction

The epitranscriptome, defined by the reversible chemical modifications of RNA, has emerged as a key area of research in molecular biology. Among more than 170 known RNA modifications, N⁶-methyladenosine (m⁶A) is the most prevalent internal modification in eukaryotic messenger RNAs. Unlike irreversible nucleotide alterations, m⁶A functions as a dynamic and reversible mark, analogous to DNA and histone modifications, providing a rapid regulatory layer for post-transcriptional regulation.

The deposition of m⁶A is catalyzed by a conserved methyltransferase (writer) complex, which in mammals consists of METTL3, METTL14, WTAP, VIRMA, and RBM15/15B, and in plants of MTA, MTB, FIP37, VIRILIZER-like proteins (VIR), and HAKAI (Fu et al. 2014). The modification occurs at the consensus DRACH motif (D = A/G/U, R = A/G, H = A/C/U), enriched around stop codons and within 3′ untranslated regions. Dynamic removal of m⁶A is catalyzed by demethylase (erasers) such as FTO and ALKBH5 in animals and ALKBH9B and ALKBH10B in plants, ensuring reversible regulation. Functional interpretation is mediated by “readers”, primarily YTH domain-containing proteins, which selectively bind methylated transcripts to influence their fate.

Functionally, m⁶A impacts virtually every stage of the mRNA life cycle. In animals, m⁶A regulates splicing, nuclear export, mRNA stability, and translation efficiency. For instance, METTL3-mediated m⁶A is essential for embryonic development, stem cell differentiation, and neuronal plasticity (Quarto et al. 2025; Thombare et al. 2024; Yang et al. 2025). In plants, m⁶A contributes to embryogenesis, meristem maintenance, leaf morphogenesis, flowering time control, and stress adaptation (Arribas-Hernandez et al. 2018; Shao et al. 2025; Sharma et al. 2023; Shen and Yu 2025). Disruption of core m⁶A writers, such as MTA or FIP37, leads to embryonic lethality (Shen et al. 2016; Vespa et al. 2004; Zhong et al. 2008), underscoring the essential role of this modification in developmental programming. For instance, Arabidopsis MTA knockdown plants exhibit impaired growth under cold conditions (8 °C) compared to the wild type, accompanied by reduced abundance and translation of m⁶A-marked transcripts (Wang et al. 2023). The cold‐responsive gene DGAT1 shows reduced translation in MTA RNAi plants, highlighting the functional relevance of m⁶A in stress adaptation. Similarly, m⁶A readers regulate gene expression through selective stabilization or sequestration of transcripts. ECT8, for example, sequesters the m⁶A-marked ABA receptor gene PYL7 into stress granules to form phase separation condensates, thereby preventing its translation and attenuating ABA signaling (Wu et al. 2024).

Beyond endogenous functions, increasing evidence reveals that m⁶A also acts as a molecular interface in host interactions with exogenous factors, including host-virus interaction. In animal viruses, m⁶A exerts diverse and context-dependent roles, including modulating viral RNA stability, nuclear export, translation, and genome packaging (McFadden and Horner 2021; Williams et al. 2019). In RNA viruses, such as flaviviruses, retroviruses, and coronaviruses, dynamic methylation and the subsequent recognition by reader proteins influence replication efficiency and immune evasion (Williams et al. 2019). For example, m⁶A enhances Human Immunodeficiency Virus Type 1 (HIV-1) RNA export and protein production (Lichinchi et al. 2016a). In contrast, m⁶A supports replication and immune escape in Zika virus and influenza A virus (Lichinchi et al. 2016b; Wang et al. 2025). Conversely, in certain contexts, m⁶A restricts viral gene expression or promotes innate immune recognition. DNA viruses, including adenoviruses and herpesviruses, also exploit m⁶A to regulate transcription, splicing, and the balance between latent and lytic infection. Notably, Kaposi’s sarcoma-associated herpesvirus employs m⁶A to control latency-associated transcripts and reactivation. In parallel, m⁶A shapes host antiviral responses by modulating interferon-stimulated genes and innate immune sensors, with viruses often reprogramming the host m⁶A machinery to their advantage. Thus, m⁶A acts as a dynamic epitranscriptomic switch in animal viruses, simultaneously representing both a vulnerability and a weapon in infection, with potential implications for antiviral strategies.

A growing body of research indicates that plant viruses are similarly influenced by host-mediated m⁶A modification (He et al. 2023b; Secco et al. 2025). Infections with viruses such as Cucumber mosaic virus (CMV) alter m⁶A deposition on both host and viral RNAs (Liu et al. 2025), suggesting that m⁶A constitutes part of the molecular arms race between plants and viruses. In this review, we systematically summarize current knowledge of m⁶A function and mechanisms in plant–virus interactions and discuss key unresolved questions and future research directions.

Validation of m⁶A modifications on plant viruses

For decades, it remained unclear whether plant viruses themselves carry this modification on their genomic or subgenomic RNAs. Since 2017, however, accumulating evidence has provided direct validation that plant viral RNAs are indeed subject to m⁶A modification (Table 1). The first biochemical evidence was reported by Martínez-Pérez et al., who used anti-m⁶A antibody–based immunoprecipitation of viral RNAs (MeRIP-qPCR) to demonstrate the enrichment of Alfalfa mosaic virus (AMV) RNAs (Martinez-Perez et al. 2017). In another study, Zhang et al. combined MeRIP-seq with a site-specific validation method to map high-confidence m⁶A peaks in Wheat yellow mosaic virus (WYMV) RNAs (Zhang et al. 2022). Similarly, Yue et al. reported that m⁶A peaks are enriched in discrete internal and 3′ terminal regions of Plum pox virus (PPV) and Potato virus Y (PVY) genomes in Nicotiana benthamiana (Yue et al. 2022). Further evidence was provided by He et al. (He et al. 2024, 2023a), who detected m⁶A in viral particles isolated from Pepino mosaic virus (PepMV)-infected tomato plants using both MeRIP-seq and dot blot analysis with anti-m⁶A antibodies.

Table 1.

Viruses identified with m⁶A modifications

Virus	Host Plant	Identification Methods	Functions	Reference
Alfalfa mosaic virus (AMV)	Arabidopsis thaliana	MeRIP-seq, LC–MS/MS	Suppresses viral systemic infection	(Martinez-Perez et al. 2023, 2017)
Barley yellow striate mosaic virus (BYSMV)	Hordeum vulgare (Barley)	MeRIP-seq, m6A-IP qPCR	Promotes viral RNA stability and infection	(Zang et al. 2025)
Pepino mosaic virus (PepMV)	Nicotiana benthamiana; Solanum lycopersicum	MeRIP-seq, dot blot	Promotes viral RNA decay	(He et al. 2024, 2023a)
Cucumber mosaic virus (CMV)	Arabidopsis thaliana	MeRIP-seq, DRS, LC–MS/MS, dot blot	Promotes viral RNA decay	(Liu et al. 2025)
Wheat yellow mosaic virus (WYMV)	Triticum aestivum	MeRIP-seq, dot blot	Stabilizes viral RNA to promote infection	(Zhang et al. 2022)
Sugarcane mosaic virus (SCMV)	Maize	MeRIP-seq, DRS, SRAMP	Promote viral RNA decay	(Peng et al. 2026)
Potato virus Y (PVY)	Nicotiana benthamiana	MeRIP-seq, dot blot	Promote viral RNA decay	(Li et al., 2026)
Bamboo mosaic virus (BaMV)	Dendrocalamus latiflorus Munro	DRS	N/A	(Li et al. 2025)
Rice stripe virus (RSV) and Rice black-streaked dwarf virus (RBSDV)	Oryza sativa	MeRIP-seq	N/A	(Zhang et al. 2021a)

Most recently, an antibody-free nanopore direct RNA sequencing (DRS) approach has been employed to identify m⁶A in viral RNAs (Li et al. 2025; Liu et al. 2025; Peng et al. 2026). Liu et al. identified the presence of m⁶A in CMV genomic RNAs was validated through a combination of antibody-dependent MeRIP-seq, antibody-independent DRS, and LC–MS/MS analysis of viral particles. Notably, DRS enables single-base resolution mapping of m⁶A sites, and the majority of sites identified by DRS overlapped with MeRIP-seq peaks, thereby strengthening the reliability of the findings. A recent study demonstrated that Sugarcane mosaic virus (SCMV), a prevalent potyvirus infecting maize, undergoes m⁶A modification during infection (Peng et al. 2026). By integrating MeRIP-seq, DRS, and the sequence-based RNA adenosine methylation site predictor tool (SRAMP), the authors identified an m⁶A modification site at A6556 within the SCMV coding sequence. Furthermore, they showed that ZmMTA directs m⁶A deposition at A6556, thereby restricting SCMV infection. Consistently, a specific synonymous mutation (mutated A6556 to G) significantly enhanced SCMV infection. In another study, 122 potential m⁶A modification sites were identified in the genome of Bamboo mosaic virus (BaMV) through DRS approach (Li et al. 2025).

Together, these studies provide compelling and convergent evidence that m⁶A is an authentic epitranscriptomic modification of diverse plant viral RNAs.

How viral genomic RNAs are recognized by host m⁶A machinery

In animal cells, m⁶A writer complexes are primarily nuclear. Many animal viruses, such as influenza virus and HIV, replicate in the nucleus, granting their RNAs direct access to the host’s m⁶A machinery that modifies host transcripts. Consequently, nuclear-replicating viral RNAs are more readily modified. Cytoplasmic RNA viruses, including flaviviruses such as Zika virus (ZIKV) and Dengue virus (DENV), were long thought to also acquire m⁶A through relocalization of the writer complex or its components to replication sites. However, this view has been challenged by recent evidence. For example, Baquero-Pérez et al. demonstrated that despite extensive investigation, Chikungunya virus (CHIKV) and DENV RNAs show no detectable m⁶A when analyzed with antibody-independent methods such as SELECT and nanopore sequencing (Baquero-Perez et al. 2024). Furthermore, depletion of m⁶A writer components had no measurable impact on infection, suggesting that m⁶A modification is not universal across cytoplasmic RNA viruses.

In contrast, plant viruses, which predominantly replicate in the cytoplasm, appear to exploit distinct mechanisms to engage host m⁶A writers. Plant m⁶A writers can relocalize from the nucleus to viral replication complexes, often mediated by direct interactions with viral proteins. For example, in wheat, the writer TaMTB translocates to cytoplasmic replication sites through interaction with the WYMV NIb protein, methylating WYMV RNA at a defined site (Fig. 1). This modification enhances RNA stability and promotes infection, whereas mutation of the methylation site reduces viral stability and pathogenicity (Zhang et al. 2022). Similarly, in CMV (Fig. 1), the viral coat protein (CP) recruits m⁶A writers to the cytoplasm via direct interaction with the core writer MTB, thereby facilitating m⁶A deposition on viral RNAs (Liu et al. 2025). In addition, during SCMV infection, a co-localization of ZmMTA with SCMV genomic RNA in cytoplasmic aggregates (Peng et al. 2026), although the detailed ZmMTA relocation mechanism remains to be investigated. Taken together, these studies indicate that while nuclear replication provides direct access to host m⁶A writers, cytoplasmic viruses employ alternative strategies such as viral protein–mediated recruitment or relocalization of writer components. Importantly, not all viruses undergo m⁶A modification, as highlighted by CHIKV and DENV, underscoring the complexity and selectivity of host–virus epitranscriptomic interactions.

Fig. 1.

Recognition of viral genomic RNAs by the plant m⁶A writer complex. During CMV infection (left panel), the CMV-encoded CP protein directly interacts with AtMTB, a core component of the Arabidopsis m⁶A writer complex, to promote the nuclear-to-cytoplasmic translocation of the m⁶A writer complex, thereby facilitating m⁶A deposition on viral RNAs and subsequent RNA decay. Similarly, during WYMV infection (right panel), the WYMV-encoded NIb protein interacts with the Triticum aestivum m⁶A writer (TaMTB) to promote cytoplasmic relocation of the m⁶A writer complex and facilitate viral RNA recognition and m⁶A deposition, thereby stabilizing viral RNA and promoting infection. Image created in BioRender. Liu, J. (2026) https://BioRender.com/7m2p4da

Distinct modes of action of m⁶A in viral infection

Control of viral RNA stability

Regulation of viral RNA stability represents a major mode of action for m⁶A, as demonstrated in multiple plant–virus systems. In CMV, hypermethylated viral RNAs are recognized by the reader protein ECT8, which directs RNA decay, possibly via the P-body RNA decay pathway, thereby restricting viral proliferation (Liu et al. 2025). Similarly, in PepMV infection of Nicotiana benthamiana (He et al. 2024), overexpression of the m⁶A writers MTA or HAKAI enhances viral RNA methylation and restricts infection, whereas deficiency in these factors reduces m⁶A levels and promotes viral accumulation. Mechanistically, m⁶A-marked viral RNAs are bound by cytoplasmic YTH-domain readers NbECT2A/2B/2C, which recruit nonsense-mediated decay (NMD) factors such as UPF3 and SMG7, leading to degradation of viral transcripts. Consistent with this pathway, PepMV RNA stability is significantly increased in NbECT2B-silenced plants, and silencing of NbUPF3 or NbSMG7 confers greater susceptibility to PepMV infection. In maize, the YTH domain-containing protein ZmECT23 recognizes viral m⁶A and destabilizes m⁶A-containing SCMV RNA through direct recruitment of the CCR4-NOT complex (Peng et al. 2026). More recently, Li et al. demonstrated that Nicotiana benthamiana writer NbMTA targets PVY genomic RNA for m⁶A deposition and promotes viral RNA degradation (Li et al. 2026).

By contrast, some viruses exploit m⁶A to enhance RNA stability and promote infection. In WYMV, the viral NIb protein recruits the wheat writer TaMTB to cytoplasmic replication sites, where site-specific m⁶A deposition stabilizes viral RNA and prevents degradation, thereby supporting viral accumulation (Zhang et al. 2022). A similar strategy is observed in the plant rhabdovirus Barley yellow striate mosaic virus (BYSMV), where the accessory gene P6 mRNA is hypermethylated (Zang et al. 2025). Loss of m⁶A deposition reduces P6 mRNA stability, resulting in a mutant virus with decreased infectivity. In barley, the m⁶A eraser HvALKBH1B acts as an antiviral factor by binding P6 mRNA into cytoplasmic condensates via liquid–liquid phase separation (LLPS). The intrinsically disordered region of HvALKBH1B is essential for both LLPS and its antiviral function.

Together, these findings highlight the dual nature of m⁶A in viral RNA stability: while m⁶A often functions as an antiviral mark that targets viral RNAs for host surveillance and decay, some plant viruses hijack the host methylation machinery to stabilize their genomes and facilitate infection. This dynamic interplay underscores the complexity of m⁶A regulation in plant antiviral defense.

Systemic movement and viral spread

Beyond RNA stability, m⁶A also regulates viral systemic movement. In AMV, the host eraser ALKBH9B removes m⁶A marks from viral RNAs, and this demethylation is required for efficient systemic infection. AMV infectivity depends on the interaction between the viral coat protein and ALKBH9B (Martinez-Perez et al. 2023, 2017). Excessive m⁶A deposition reduces phloem transport, thereby restricting long-distance spread (Zhang et al. 2021b). Thus, a balanced level of m⁶A is essential for efficient viral spread. Supporting this model, infection with PPV and PVY results in a global reduction of m⁶A levels in N. benthamiana, and down-regulation of ALKBH9 homologs significantly decreases PPV and PVY accumulation (Yue et al. 2022).

In addition to erasers, host reader proteins also regulate systemic infection. YTHDF proteins ECT2, ECT3, and ECT5 bind AMV RNAs in an m⁶A-dependent manner, functioning as restriction factors that suppress viral accumulation (Martinez-Perez et al. 2023). Interestingly, the regulation of AMV infectivity appears specific to ALKBH9B, since disruption of related homologs ALKBH9A or ALKBH9C does not affect viral infection (Martinez-Perez et al. 2021).

Collectively, these findings demonstrate that m⁶A modulates not only the stability of viral RNAs but also their capacity for systemic movement, with both host writers and erasers playing crucial yet context-dependent roles in shaping infection outcomes.

Viral countermeasures against host m⁶A machinery

In the evolutionary arms race between plants and viruses, antiviral defense mechanisms are frequently counteracted by viral inhibitory strategies. Recent studies have demonstrated that viruses can actively manipulate m⁶A deposition on their genomes to attenuate host defense responses. Liu et al. (Liu et al. 2025) showed that during CMV infection, the viral 2b protein, a well-characterized suppressor of RNA silencing, suppresses m⁶A deposition on viral RNAs by impairing the function of the host m⁶A machinery (Fig. 2). Mechanistically, 2b competitively interacts with host m⁶A writer components HAKAI and MTB. Consequently, compared with wild-type plants, m⁶A-deficient plants exhibited increased susceptibility to 2b-deficient CMV but not to wild-type CMV. Furthermore, the 2b-deficient virus displayed significantly higher m⁶A levels than the wild-type virus. These findings reveal a mutually antagonistic interplay between m⁶A-mediated antiviral immunity and a viral countermeasure, positioning m⁶A dynamics as a critical battleground in the molecular arms race between plant hosts and viruses. Notably, 2b expression also exerts a profound inhibitory effect on global m⁶A levels in host plants.

Fig. 2.

Mechanisms of viral antagonism in plant m⁶A-mediated antiviral defense. A During CMV infection, the CMV-encoded 2b protein competitively binds to the Arabidopsis m⁶A writer components MTB and HAKAI, thereby impairing the integrity and functionality of the m⁶A writer complex in both the nucleus and cytoplasm. This interaction suppresses m⁶A deposition on viral RNAs as well as host defense-related transcripts. B During PepMV infection, the viral RdRP protein interacts with the m⁶A writer SlHAKAI and the tomato autophagy-related protein SlBeclin1, leading to the formation of cytoplasmic interaction granules and facilitating autophagic degradation of SlHAKAI. Consequently, m⁶A deposition of viral RNAs is inhibited, resulting in enhanced viral RNA stability. C During SCMV infection, the maize m⁶A writer ZmMTA deposits m⁶A modification on viral RNA. These m⁶A marks are recognized by the reader protein ZmECT23, which recruits the CCR4-NOT complex to promote viral RNA degradation and thereby attenuating viral infection. In contrast, the viral protien NIa-Pro hijacks the host ZmeIF4A3 factor to the viral replication complex, inhibiting ZmMTA-mediated m⁶A deposition on viral RNA and promoting viral replication. Image created in BioRender. Liu, J. (2026) https://BioRender.com/wo81sl8

In a separate study, He et al. reported that PepMV encodes a viral RNA-dependent RNA polymerase (RdRP) that promotes autophagy-dependent degradation of SlHAKAI, a core m⁶A writer component in Solanum lycopersicum (He et al. 2023a). Overexpression of SlHAKAI significantly restricted PepMV infection, underscoring its antiviral role. Mechanistically, PepMV RdRP directly interacts with SlHAKAI, inhibiting its protein accumulation via autophagic degradation. The autophagy-related protein SlBeclin1 has been shown to interact with the RdRPs of several RNA viruses and promotes their degradation (Li et al. 2018a). He et al. further revealed that the PepMV RdRP-mediated autophagic degradation of SlHAKAI requires SlBeclin1. RdRP, SlHAKAI, and SlBeclin1 form cytoplasmic interaction granules that facilitate autophagic degradation of SlHAKAI (Fig. 2). This process effectively reduces m⁶A methylation on viral RNAs, thereby enabling PepMV to evade m⁶A-mediated antiviral defenses.

More recently, Peng et al. revealed a sophisticated m⁶A-mediated antagonistic mechanism between maize and SCMV (Peng et al. 2026). On the one hand, the host m⁶A writer ZmMTA deposits m⁶A marks on SCMV genomic RNA, promoting viral RNA decay through ZmECT23-mediated recruitment of the host ZmCCR4-NOT deadenylation complex (Fig. 2). On the other hand, the SCMV nuclear inclusion protein a protease (NIa-Pro) hijacks the maize eukaryotic initiation factor 4A-III (ZmeIF4A3) into viral replication complexes, thereby blocking ZmMTA-mediated m⁶A deposition and preventing viral RNA from degradation (Fig. 2).

Collectively, these bidirectional regulatory mechanisms exemplify the dynamic interplay between host m⁶A-dependent antiviral defenses and viral strategies to subvert epitranscriptomic control.

The impacts of viral infection on host m⁶A homeostasis

Beyond substantial modification of viral genomes by the host m⁶A machinery, viral infection also profoundly alters N⁶-methyladenosine (m⁶A) RNA methylation dynamics in plant hosts. Many plant viruses induce genome-wide remodeling of the host m⁶A methylome, leading to either hypermethylation or hypomethylation of host mRNAs depending on the virus–host context.

In Nicotiana tabacum, infection with Tobacco mosaic virus (TMV) results in decreased m⁶A levels in host mRNAs, which correlates with upregulation of the putative m⁶A eraser NbALKBH5 and reduced expression of m⁶A writer components (Li et al. 2018b). Similarly, in N. benthamiana, infection by PPV and PVY reduces m⁶A levels (Yue et al. 2022). By contrast, in rice plants infected with Rice stripe virus (RSV) or Rice black-streaked dwarf virus (RBSDV), host mRNA m⁶A levels are enriched (Zhang et al. 2021a). Notably, although both infections alter global m⁶A abundance, the specific m⁶A “peaks” (sites of modification) differ, indicating virus-specific reprogramming of the host epitranscriptome.

Distinct temporal and genotype-dependent responses have also been observed. In watermelon infected with Cucumber green mottle mosaic virus (CGMMV), susceptible plants showed increased m⁶A levels at 24 h post-infection, whereas resistant cultivars exhibited decreased levels by 48 h (He et al. 2021). In Arabidopsis thaliana infected with CMV, global m⁶A levels were markedly reduced, primarily due to inhibition of the host m⁶A writer complex by the viral 2b protein (Liu et al. 2025). Supporting this mechanism, transgenic expression of 2b alone led to a significant decrease in global m⁶A levels, while infection by viruses lacking 2b had no effect, underscoring the importance of specific viral proteins in perturbing host m⁶A homeostasis.

These alterations in m⁶A profoundly affect the expression of host genes involved in immunity, hormone signaling (e.g., salicylic acid, jasmonic acid), and stress responses, thereby reshaping antiviral defense networks. In rice infected with RSV or RBSDV, virus-induced m⁶A hypermethylation is enriched in transcripts associated with RNA silencing and hormone-mediated defense pathways, including antiviral genes such as OsAGO18 and OsSLRL1 (Zhang et al. 2021a). The extent of m⁶A methylation is closely correlated with changes in transcript abundance, and the effects of m⁶A modifications differ by gene region. Similar reprogramming occurs in CGMMV-infected watermelon, where susceptible plants exhibited early global m⁶A hypermethylation of stress- and defense-related transcripts, whereas resistant plants displayed later hypomethylation that preserved defense gene expression (He et al. 2021). In A. thaliana, CMV-induced m⁶A hypomethylation primarily resulted in the upregulation of immune genes, including NPR3 and CBP60a, which are key regulators in salicylic acid-mediated defense (Liu et al. 2025). In Nicotiana benthamiana, infection by PVY induces dynamic alterations in global m⁶A levels, which are elevated during the early to middle stages of infection (5–10 days post-inoculation, dpi) but decline by 14 dpi (Li et al. 2026). PVY infection enhances the expression of the m⁶A-modified transcription factor NFYA3_0, which in turn activates transcription of the m⁶A writer NbMTA, thereby promoting m⁶A deposition on viral RNAs and accelerating viral RNA degradation. Li et al. demonstrated that BaMV infection induces a global increase of m⁶A levels in D. latiflorus accompanied with reduced proportion of full-length transcripts (Li et al. 2025). Epitranscriptome analysis showed increased m⁶A ratios in the chlorophyll synthesis genes POR and abscisic acid synthesis gene NCED1, which coupled with reduced transcriptional levels.

Collectively, these findings highlight that viral infection reprograms the host epitranscriptome and that dynamic m⁶A regulation acts as a fine-tuning mechanism in plant-virus interactions.

Perspective

In plants, the dynamic interplay between m⁶A deposition and viral counterstrategies defines a key battleground of molecular plant immunity, offering potential leverage points for crop improvement and antiviral strategies. The emerging view of m⁶A as a pivotal regulator in plant–virus interactions highlights an additional epitranscriptomic layer of complexity in plant pathology. While initially characterized for its developmental roles, recent discoveries demonstrate that m⁶A marks on both host and viral RNAs actively shape the interaction between viral infection and host adaptation. Plant viruses, many of which replicate exclusively in the cytoplasm, rely on the capacity of the host m⁶A machinery to relocalize or be recruited to replication sites, thereby enabling the modification of viral genomes. These modifications can either restrict or promote infection depending on the specific virus-host context. For instance, in PepMV, hypermethylation of viral RNA triggers recognition by host YTH-domain readers and subsequent RNA decay, whereas in WYMV, recruitment of TaMTB by the viral NIb stabilizes viral transcripts and enhances accumulation. These findings underscore the dual role of m⁶A as both an antiviral defense strategy and a viral exploitation mechanism.

Equally important is the systemic dimension of m⁶A regulation. In AMV, balanced demethylation by ALKBH9B is required for efficient long-distance movement, illustrating that m⁶A does not act in a binary restrictive or permissive manner but instead fine-tunes infection dynamics to optimize viral spread. Moreover, virus-induced perturbations of host m⁶A homeostasis exert broad effects on transcriptome reprogramming. Distinct viruses remodel global methylation landscapes differently. CMV, TMV, and PPV induce hypomethylation of host mRNAs, while RSV and RBSDV increase methylation levels. These changes extend beyond individual transcripts to influence entire regulatory pathways, including hormone signaling and RNA silencing, thereby integrating m⁶A into the host’s broader stress and developmental networks.

The antagonistic interplay between host defenses and viral countermeasures adds further complexity. Viral proteins such as CMV 2b and PepMV RdRP directly target host m⁶A writers, either by competitive inhibition or by promoting autophagic degradation of core components. These strategies effectively suppress m⁶A deposition on viral RNAs, allowing viruses to evade restriction. In turn, plants have evolved erasers such as HvALKBH1B, which sequester and destabilize viral transcripts via liquid–liquid phase separation (Zang et al. 2025). The reciprocal adaptation of host and virus demonstrates that m⁶A is a central node in the molecular arms race of infection.

Looking forward, several key questions remain open. First, recent methodological studies have drawn attention to potential limitations in transcriptome-wide m⁶A detection. Notably, a recent report showed that false-positive m⁶A signals may occur not only in antibody-based m⁶A-RIP-seq but also in certain antibody-independent detection approaches, highlighting the necessity of appropriate negative controls and careful data interpretation (Pan et al. 2025). These observations suggest that current m⁶A mapping strategies may still be susceptible to technical artifacts, particularly when applied to complex biological samples. Looking forward, emerging technologies such as single-molecule and real-time RNA modification mapping are expected to improve the resolution and specificity of m⁶A detection. The continued development and integration of such approaches will be important for refining epitranscriptomic landscapes and for achieving more accurate and quantitative characterization of RNA modifications in diverse systems. Second, how are specific viral or host transcripts selectively targeted for m⁶A deposition or removal during infection? The identification of sequence and structural determinants will be essential to predict outcomes across different plant–virus systems. Third, what are the temporal dynamics of m⁶A reprogramming? Time-resolved mapping may reveal whether early infection stages favor antiviral methylation, while later stages are dominated by viral suppression mechanisms. Fourth, can the manipulation of m⁶A pathways be exploited for durable crop resistance? Overexpression of writer components or modulation of reader activity has shown promise in experimental systems, suggesting the potential for breeding or biotechnological strategies.

In conclusion, m⁶A represents a versatile regulatory hub that integrates viral replication strategies with host RNA metabolism. Its context-dependent roles, as both a host defense mechanism and a viral advantage, reflect its dynamic nature as an epitranscriptomic switch. A deeper mechanistic understanding of this modification in the plant-virus system holds promise for novel antiviral approaches and offers a paradigm for studying RNA modifications in complex host–pathogen interactions.

Authors’ contributions

J.H.L., H.Y., and C.G.D. conceived the study and wrote the manuscript.

Funding

This study was supported by the State Key Laboratory of Plant Trait Design.

Data availability

No datasets were generated or analyzed during the current study.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

All authors agreed with the content and that all gave explicit consent to submit.

Competing interests

Hao Yu is a member of the Editorial Board for Advanced Biotechnology but he is not involved in the journal’s review and decisions related to this manuscript.