Noncoding RNAs and the phytochemical economy: Molecular regulators of secondary metabolism in medicinal plants

Abstract

Background: Medicinal plants produce specialised (secondary) metabolites including alkaloids, terpenoids, flavonoids and phenolics that underpin pharmaceuticals, nutraceuticals and traditional therapeutics. Although enzyme-encoding genes and transcription factors are established regulators of these pathways, accumulating evidence indicates that noncoding RNAs (ncRNAs) provide additional, and in some contexts decisive, regulatory control. Objective: To synthesise and critically appraise evidence on how plant ncRNAs microRNAs (miRNAs), small interfering RNAs (siRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) regulate secondary metabolism in medicinal plants, and to map translational opportunities and unresolved gaps. Methods: We conducted a narrative review with a systematic synthesis across PubMed/MEDLINE, Scopus, Web of Science Core Collection, CAB Abstracts and AGRICOLA, supplemented by Google Scholar screening using SANRA. Results: Across medicinal and non-model plant systems, miRNAs repeatedly target transcription factors that control biosynthetic pathways (e.g., MYB/bHLH/WRKY families) and, in some cases, key enzymes (e.g., PAL/CHS/DFR modules), thereby supporting stress-responsive and developmentally timed reprogramming of metabolite profiles. siRNAs contribute through RNA-directed DNA methylation (RdDM) and regulation of transposons and gene clusters. lncRNAs modulate chromatin accessibility and function as scaffolds or decoys, including as competing endogenous RNA (ceRNA) 'sponges', whereas circRNAs are emerging as relatively stable regulatory hubs that may influence miRNA availability and stress-associated transcriptional states. Evidence quality varies across ncRNA classes and species, and mechanistic validation in medicinal plants remains inconsistent. Conclusions: ncRNAs constitute a multilayer regulatory system shaping the 'phytochemical economy' of medicinal plants. Progress towards translation will require standardised ncRNA annotation resources, rigorous causal validation, and integrated multi-omics study designs to support precision metabolic engineering and sustainable phytochemical production.