Recent advances in ethnobotanical and neurological research indicate that ingested plants from our diet may not only be a source of nutrition but also a source of biologically relevant nucleic-acid-encoded genetic information. A major source of RNA-encoded information from plants has been shown to be derived from small non-coding RNAs (sncRNAs) such as microRNAs (miRNAs) that can transfer information horizontally between plants and humans. In human hosts, the 3'-untranslated region (3'-UTR) of messenger RNAs (mRNAs) is targeted by these miRNAs to effectively down-regulate expression of that mRNA target in the host CNS. In this paper, we provide evidence that the Atropa belladonna aba-miRNA-9497 (miRBase conserved ID: bdi-miRNA-9497) is highly homologous to the CNS-abundant Homo sapiens miRNA-378 (hsa-miRNA-378) and both target the zinc-finger transcription factor ZNF-691 mRNA 3'-UTR to down-regulate ZNF-691 mRNA abundance. We speculate that the potent neurotoxic actions of the multiple tropane alkaloids of Atropa belladonna may be supplemented by the neuroregulatory actions of aba-miRNA-9497 on ZNF-691, and this may be followed by the modulation in the expression of ZNF-691-sensitive genes. This is the first example of a human brain-enriched transcription factor, ZNF-691, targeted and down-regulated by a naturally occurring plant microRNA, with potential to modulate gene expression in the human CNS and thus contribute to the neurotoxicological-and-psychoactive properties of the Atropa belladonna species of the deadly nightshade Solanaceae family.
Keywords: Atropa belladonna; Atropine; Trans-kingdom miRNA signaling; Zinc-finger protein ZNF-691; aba-miRNA-9497; hsa-miRNA-378.