Cross-Kingdom Regulation by Plant MicroRNAs

Plant microRNAs are small non-coding RNAs that regulate gene expression within the plant kingdom and, remarkably, can traverse biological barriers to exert effects in animal hosts. Following ingestion, certain plant microRNAs withstand digestive processes, enter circulation via specialised uptake mechanisms and associate with cellular machinery to modulate target messenger RNAs in distant tissues. This phenomenon of cross-kingdom regulation has transformed our understanding of diet–host interactions, revealing that bioactive plant RNAs may act as dietary signalling molecules with hormone-like functions. Central questions now address the pathways of absorption, the molecular carriers that protect these molecules in transit and the breadth of processes—from immune modulation to metabolic control—affected by exogenous plant miRNAs. The global significance spans agricultural biotechnology, nutrition science and the development of orally delivered nucleic acid therapies. As the field matures, rigorous characterisation of delivery vehicles, receptor-mediated uptake and off-target effects will be essential to translate these insights into practical applications in human and veterinary health.

Research from Nature Portfolio

Recent investigations have demonstrated that plant microRNAs can directly influence mammalian immune responses. Synthetic or native plant miRNA fractions introduced to dendritic cells attenuate inflammatory signalling by engaging Toll-like receptor 3 and impairing downstream pathways, thereby limiting T-cell proliferation and reducing autoimmune pathology in vivo. This immunomodulatory capacity suggests therapeutic potential for plant miRNAs in chronic-inflammation disorders.

In a porcine model, heat-stable maize microRNAs surviving conventional cooking were detected in serum, tissues and immune cells after dietary exposure. These plant-derived miRNAs not only crossed the gastrointestinal barrier but also bound endogenous porcine mRNAs to modulate gene expression in a manner analogous to endogenous animal miRNAs. The study highlights both the resilience of dietary plant miRNAs and their capability to regulate vertebrate gene networks.

Cross-Kingdom Regulation by Plant MicroRNAs publication trend

The graph below shows the total number of articles in cross-kingdom regulation by plant micrornas across all publications each year (not limited to Nature Index journals).

Technical terms

microRNA (miRNA): A small (~21–24 nucleotide) non-coding RNA molecule that binds complementary sequences in messenger RNA to repress translation or induce degradation.

Cross-kingdom regulation: The transfer and functional activity of regulatory molecules, such as miRNAs, from one biological kingdom (e.g., plants) to another (e.g., animals).

Exosome: A membrane-bound extracellular vesicle that transports proteins, lipids and RNAs between cells, protecting cargo from degradation.

Decoctosome: A plant-derived nanoparticle formed during herbal decoction, rich in bioactive small RNAs and other molecules, used for oral nucleic acid delivery.

Bencaosome: An engineered form of decoctosome with enriched small RNA content, designed to enhance therapeutic delivery of nucleic acids.

References

1. Nanoparticles derived from herbal preparations May represent a novel nucleic acid therapy. Interdisciplinary Medicine (2024).
2. MicroRNAs from plants to animals, do they define a new messenger for communication?. Nutrition & Metabolism (2018).
3. Plant microRNAs as novel immunomodulatory agents. Scientific Reports (2016).
4. Detection of dietetically absorbed maize-derived microRNAs in pigs. Scientific Reports (2017).