The Hidden Code of RNA: How Epitranscriptomic Modifications Are Reshaping Our Understanding of Plant Biology

Most biologists are familiar with epigenetics: DNA methylation, histone modification, chromatin remodelling. These mechanisms have shaped our understanding of how gene expression is regulated beyond the primary nucleotide sequence. But over the past decade, an analogous regulatory layer has emerged for RNA, and its implications for plant biology are only beginning to come into focus. Chemical modifications of RNA, collectively termed the epitranscriptome, constitute a dynamic, reversible system of post-transcriptional gene regulation. Over 160 distinct chemical modifications have been identified on RNA, although only a handful have been functionally characterized in plants. Among these, N6-methyladenosine (m6A) has taken centre stage, but 5-methylcytosine (m5C), N4-acetylcytidine (ac4C), and pseudouridine (Ψ) are rapidly gaining recognition as important regulators of RNA metabolism. What makes this field especially exciting for plant science is the growing body of evidence that these modifications govern the traits breeders care most about: yield, flowering time, fruit ripening, seed germination, and stress resilience.

m6A is the most abundant internal modification of polyadenylated RNA. Extensive work into the role of m6A has implicated this modification in all areas of plant development from seed to seed, and as a mediator or abiotic and biotic stress . Further elucidation of m6A has enormous potential in improving trait quality in plants. 1 2 5-methylcytosine (m5C) on mRNA has been implicated in long-distance transcript transport in plants, a process critical for systemic signalling and graft-transmissible effects on development . m5C also appears to influence mRNA stability and translational output, with potential downstream consequences for organ development and stress adaptation.

N4-acetylcytidine (ac4C) is an emerging mark that appears to enhance the translational efficiency of target transcripts. Recent work indicates that ac4C contributes to stress resilience by optimizing protein production under adverse conditions such as drought or pathogen attack; conditions when translational reprogramming is most consequential .3 Pseudouridine (Ψ), the isomerization of uridine into a more thermodynamically stable form, is the most abundant RNA modification overall, but its role in plant mRNAs has lagged behind other modifications. Emerging evidence suggests that Ψ levels increase under stress and may enhance the stability and translational competence of transcripts .4 The interplay among these modifications, whether they cooperate, compete, or act independently on shared targets, remains an open and critical question. In the coming years, the distribution and type of RNA modification are likely to become as important as the relative abundance of desired transcripts when researchers consider optimizing plant species for ideal traits. With the cost of high-throughput RNA sequencing falling dramatically year-over-year, I’m hopeful that researchers will continue to innovate exciting ways to identify the presence of unique RNA modifications, and further understand the implication of epitranscriptomics in gene regulation.

Further Reading

1. Kim, J., Shim, S., Lee, H., and Joon, P. (2020). m6A mRNA Modification as a New Layer of Gene Regulation in Plants. J. Plant Biol. 63, https://doi.org/10.1007/s12374-020-09239-5. 97–106.

2. Lei, Y., Perrera, V., Saplaoura, E., Apelt, F., Bahin, M., Kramdi, A., Olas, J., Roeber-Mueller, B., Sokolowska, E., Zhang, W., et al. (2019). m5C Methylation Guides Systemic Transport of Messenger RNA over Graft Junctions in Plants Article m 5 C Methylation Guides Systemic Transport of Messenger RNA over Graft Junctions in Plants. Curr. Biol. 29, 2465–2476. https://doi.org/10.1016/j.cub.2019.06.042.

3. Yao, J., Xiao, G., Ma, X., Hui, S., Shang, H., Zhang, J., and Xu, Q. (2025). The emerging epitranscriptomic modification ac4C regulates plant development and stress adaptation. Nat. Plants 11, 2200–2203. https://doi.org/10.1038/s41477-025-02140-4.

4. Niu, Y., and Liu, L. (2023). RNA pseudouridine modification in plants. J. Exp. Bot. 74, 6431–6447.