Highlights

• The study is the first to show that a tRNA-derived fragment from ginseng can act as a potent RNA therapeutic by directly targeting a disease-related lncRNA (MIAT) in heart injury.
• The research introduces a novel approach by constructing a double-stranded tRF_mimic (HC83_mimic), enhancing its stability and gene-silencing efficiency compared to single-stranded forms.
• It reveals a new regulatory pathway in ischemic heart disease involving HC83-mediated downregulation of MIAT and subsequent upregulation of VEGFA, offering a new therapeutic target beyond mRNA.

Summary

This research article investigates a novel therapeutic approach for ischemic heart disease using a tRNA-derived fragment (tRF) from ginseng.

The study identifies a 22-nucleotide RNA fragment named HC83, which significantly enhances cardiomyocyte survival under hypoxic conditions and shows over 500-fold stronger effects than metoprolol in vivo.

Mechanistically, HC83 targets and suppresses the long non-coding RNA MIAT, resulting in the upregulation of VEGFA, a key factor in cardiac protection and angiogenesis. This tRF not only preserves mitochondrial function and cytoskeletal integrity but also mitigates oxidative stress and calcium overload during reperfusion injury.

The findings suggest that ginseng-derived tRFs may serve as highly potent RNA-based therapeutics and offer a new strategy for discovering RNA drugs from traditional Chinese medicine

K. Hu et al., “A tRNA-derived fragment of ginseng protects heart against ischemia/reperfusion injury via targeting the lncRNA MIAT/VEGFA pathway,” Molecular Therapy – Nucleic Acids, vol. 29, pp. 672–688, Sep. 2022, doi: 10.1016/j.omtn.2022.08.014.