Drug discovery from plants usually focuses on small molecules rather than such
biological macromolecules as RNAs. Although plant
transfer RNA (
tRNA)-derived fragment (tRF) has been associated with the developmental and defense mechanisms in plants, its regulatory role in mammals remains unclear. By employing a novel reverse
small interfering RNA (
siRNA) screening strategy, we show that a tRF mimic (antisense derived from the 5' end of
tRNAHis(GUG) of Chinese yew) exhibits comparable anti-
cancer activity with that of
taxol on
ovarian cancer A2780 cells, with a 16-fold lower dosage than that of
taxol. A dual-
luciferase reporter assay revealed that tRF-T11 directly targets the
3' UTR of oncogene TRPA1
mRNA. Furthermore, an Argonaute-
RNA immunoprecipitation (AGO-RIP) assay demonstrated that tRF-T11 can interact with AGO2 to suppress TRPA1 via an RNAi pathway. This study uncovers a new role of plant-derived tRFs in regulating endogenous genes. This holds great promise for exploiting novel
RNA drugs derived from nature and sheds light on the discovery of unknown molecular targets of
therapeutics.