Anti-tumor effects of an engineered “killer” transfer RNA

A hallmark of cancer cells is their ability to continuously divide; and rapid proliferation requires increased protein translation. Elevating levels of misfolded proteins can elicit growth arrest due to ER stress and decreased global translation. Failure to correct prolonged ER stress eventually results in cell death via apoptosis. tRNASer(AAU) is an engineered human tRNASer with an anticodon coding for isoleucine. Here we test the possibility that tRNASer(AAU) can be an effective killing agent of breast cancer cells and can effectively inhibit tumor-formation in mice. We found that tRNASer(AAU) exert strong effects on breast cancer translation activity, cell viability, and tumor formation. Translation is strongly inhibited by tRNASer(AAU) in both tumorigenic and non-tumorigenic cells. tRNASer(AAU) significantly decreased the number of viable cells over time. A short time treatment with tRNASer(AAU) was sufficient to eliminate breast tumor formation in a xenograft mouse model. Our results indicate that tRNASer(AAU) can inhibit breast cancer metabolism, growth and tumor formation. This RNA has strong anti-cancer effects and presents an opportunity for its development into an anti-tumor agent. Because tRNASer(AAU) corrupts the protein synthesis mechanism that is an integral component of the cell, it would be extremely difficult for tumor cells to evolve and develop resistance against this anti-tumor agent.

► tRNA with anti-cancer effects.
► tRNA induced protein misfolding.
► tRNA as anti-tumor agent.