Transfer ribonucleic acid (tRNA)

Transfer ribonucleic acids (tRNAs) are essential non-coding adapter molecules that translate the genetic information in messenger RNA (mRNA) into specific amino acid sequences during protein synthesis. In cancer cells, the tRNA pool is frequently reprogrammed and upregulated to meet the high metabolic and proliferative demands of the tumor, often through the selective overexpression of specific tRNA isoacceptors that favor the translation of pro-oncogenic transcripts (Pavon-Eternod et al., 2009). Beyond their primary role in translation, tRNAs serve as precursors to tRNA-derived fragments (tRFs), which act as regulatory molecules similar to microRNAs, influencing gene silencing, RNA stability, and cell survival pathways (Goodarzi et al., 2015). Therapeutic targeting of the tRNA machinery in cancer involves inhibiting tRNA-modifying enzymes like NSUN2 or METTL1, or targeting aminoacyl-tRNA synthetases with drugs like Halofuginone to induce amino acid starvation responses and selective apoptosis in malignant cells (Huang et al., 2021). Furthermore, established chemotherapeutics such as 5-fluorouracil exert significant anti-tumor activity by incorporating into tRNAs and disrupting essential post-transcriptional modifications, thereby impairing the stability and function of the translational apparatus (Gkatza et al., 2019).

Other names

tRNATransfer RNASoluble RNAsRNAAdapter RNA

Inhibition of tRNA-modifying enzymes to disrupt translational fidelity, competitive inhibition of aminoacyl-tRNA synthetases to trigger the integrated stress response, and modulation of tRNA-derived fragments (tRFs) to interfere with oncogenic signaling.