Highlights

• This is the first study to isolate and chemically characterize a native tRNA from fungus, specifically Ganoderma lucidum.
• The researchers identified 3′-tRNA halves as potent anticancer components, with cytotoxicity stronger than current small-molecule standards like taxol.
• The study revealed that m5U modification enhances both the structural stability and biological activity of a tRNA-derived fragment, supporting its relevance in RNA drug design.

Summary

The study investigates a newly identified transfer RNA, tRNAIle(GAU), extracted from Ganoderma lucidum, a traditional medicinal fungus, and explores its anti-cancer potential.

Researchers discovered that fragments derived from this tRNA, especially a 3′-tRNA half (3′-t-half) mimic, displayed potent cytotoxic effects on several cancer cell lines, surpassing even well-known anti-cancer agents like taxol and ganoderic acids. Using mass spectrometry and computational modeling, they identified post-transcriptional modifications in the tRNA, notably 5-methyluridine (m5U), which enhanced the stability of the fragment’s tertiary structure and significantly increased its cytotoxic activity. These findings suggest that RNA molecules in Ganoderma, previously overlooked, could be important bioactive components with therapeutic potential.

The research highlights a new role for m5U modifications in modulating the biological activity of RNA fragments, offering insights for the development of RNA-based anti-cancer drugs.

F. Ren et al., “The role of post-transcriptional modification on a new tRNAIle(GAU) identified from Ganoderma lucidum in its fragments’ cytotoxicity on cancer cells,” International Journal of Biological Macromolecules, vol. 229, pp. 885–895, Feb. 2023, doi: 10.1016/j.ijbiomac.2022.12.327.