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tRNAs as Therapeutic Agents of Breast Cancer

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Final rept. 1 Jul 2012-30 Jun 2013

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Transfer RNAs tRNA are small non-coding RNAs that read the genetic codes in protein synthesis. It is essential for the proliferation, fitness and adaptation of the cell that each tRNA is aminoacylated charged with its designated amino acid. The utilization of mischarged tRNAs i.e. tRNAs with incompatibly charged amino acid and decoding capacity leads to the synthesis of mutated proteins that can fold incorrectly. Accumulation of misfolded proteins in the cell activates an integrated cellular mechanism, the Unfolded Protein Response which dictates cell fate in response to the amount of misfolded proteins. High accumulation of misfolded proteins derived from the cellular presence of mischarged tRNAs can therefore induce apoptosis of the cell. We aim to engineer tRNAs that are always mischarged in a human cell and study their effects on breast tumor cell physiology and cell death. Protein demand in rapidly proliferating cells is extremely high and small defects during cellular protein synthesis caused by the presence of such tRNAs can have a strong impact on both tumor invasiveness and survival. Ultimately, we aim to demonstrate that these mischarged tRNAs can be developed as a novel class of RNA-based agents to treat breast tumors.

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  • Anatomy and Physiology
  • Medicine and Medical Research

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