Insights into the role of N6-methyladenosine (m6A) in plant-virus interactions

Abstract

N6-methyladenosine (m6A) is a common and dynamic epitranscriptomic modification in eukaryotic RNAs, affecting stability, splicing, translation, and degradation. Recent technological advancements have revealed the complex nature of m6A modifications, highlighting their importance in plant and animal species. The m6A modification is a reversible process, with "writers" depositing methylation, "erasers" demethylating it, and "reader" proteins recognizing m6A and executing various biological functions. Studying the relationship between m6A methylation and viral infection is crucial. Animal viruses, including retroviruses, RNA viruses, and DNA viruses, often employ the host's m6A machinery to replicate or avoid immune responses. In plant viruses, host methyltransferases or demethylases can stabilize or degrade viral RNA, depending on the virus-host interaction. Additionally, viral infections can modify the host's m6A machinery, impacting the viral life cycle. This review examines the role of m6A modifications in plant viral pathogenesis, focussing on RNA viruses infecting crops like alfalfa, turnip, wheat, rice, and potato. Understanding the role of m6A in virus-host interactions can aid in studying plant viral disease development and discovering novel antiviral targets for crop protection. In this review, we summarize current information on m6A in RNA biology, focussing on its function in viral infections and plant-virus interactions.

Keywords: RNA modification; m6A; plant virus.

Fig 1

Schematic representation of the methylation process: most eukaryotic mRNAs and lcRNAs are methylated in the nucleus, costranscriptionally. Although some reader proteins are nuclear localized and can exercise their activity directly in the nucleus, most reader proteins are cytoplasmic and need the m6A labeled RNA to exit the nucleus. Eraser proteins are found in both the nucleus and cytoplasm, and they are shown only in the latter since most of the erasers described in this work are cytoplasmic.

Fig 2

AMV vRNAs contain several m6A peaks. Host ECT proteins recognize and bind m6A marks on vRNAs, leading them to degradation. Conversely, the host eraser protein ALKBH9B interacts with the viral coat protein (CP) and demethylates vRNAs, thereby promoting viral replication. The actual impact of ALKBH9B and Cp interaction remains unclear.

Fig 3

Mechanisms used by viruses to evade m6A-based defenses. (A) TMV, PPV, and PVY cause host m6A levels to drop significantly during the infection. Downregulation or mutations in the host ALKB enzymes cause a reduction in viral titer and impede viral replication and proliferation. (B) Schematic representation of PepMV strategy to evade plant m6A modifications by directing HAKAI toward autophagic degradation.

Fig 4

WYMV replication and virulence are positively influenced by host m6A methylation. In susceptible wheat varieties, the viral NIb protein binds to the host MTB protein, causing its relocalization to the cytoplasm, where it enhances vRNA methylation, promoting viral replication. In contrast, this interaction is disrupted in resistant wheat varieties resulting in significantly reduced vRNA methylation. This difference is attributed to a SNP at position 176, distinguishing sensitive ("S") from resistant ("R") wheat varieties.