Computational Analysis of Conserved Plant microRNA408 and Evaluation of its Cross-Kingdom Regulatory Potential in Humans

Souraja Mitra and Lata I Shukla*

Introduction: MicroRNA408 (miRNA408) is a highly conserved plant microRNA involved in copper homeostasis, development, and stress response. Given its presence in food crops and its evolutionary conservation, this study explores in silico analysis of mature and precursor miRNA408 (pre-miRNA408) and whether miRNA408 could exert post-transcriptional regulatory effects on human genes via dietary cross-kingdom interaction.

Methodology: A total of 72 mature and 55 precursor miRNA408 sequences were retrieved from miRBase v22. Sequence conservation, alignment, and phylogeny were analyzed using WebLogo, MAFFT, and iTOL, respectively. RNAfold was used to assess thermodynamic stability. A consensus miR408-3p sequence obtained from the literature was used to predict human gene targets via psRNATarget. Only targets predicted to be cleaved were selected for validation based on alignment, seed complementarity, and 3′compensatory sites pairing.

Results: The 3p strand exhibited higher nucleotide conservation than the 5p strand. Most mature sequences began with adenosine, suggesting AGO2–AGO9 loading. Longer precursors displayed lower minimum free energy (MFE), indicating higher structural stability. The high-confidence human target genes are involved in critical processes like gene regulation, cytoskeletal organization, neural development, and intracellular transport, highlighting the potential for dietary miRNAs to influence human biology.

Conclusion: miR408 has been reported in dietary plants such as tomato (Solanum lycopersicum). Multiple studies support the uptake and activity of dietary miRNAs in mammals. This study provides computational evidence for miR408’s cross-kingdom regulatory potential, which requires further experimental validation.

Keywords:

Published on: Nov 6, 2025 Pages: 1-15

Full Text PDF Full Text HTML DOI: 10.17352/amgm.000015
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