tRNA dosage regulates lineage dependency and resistance in prostate cancer.

tRNA 1 Arg (UCU) regulates lineage transitions and therapy resistance in prostate cancer by controlling a chromatin remodeling translational program.

• Why it matters: Understanding the mechanisms behind lineage plasticity and therapy resistance in cancer is crucial for developing more effective treatments, especially in prostate cancer where resistance limits current options.
• What they did: Researchers performed unbiased small RNA sequencing in prostate cancer models and identified tRNA 1 Arg (UCU) as a key regulator; they also studied its regulation by TARDBP and ZSCAN29 and its role in maintaining lineage fidelity through SWI/SNF chromatin remodellers.
• The result: Downregulation of tRNA 1 Arg (UCU) in neuroendocrine prostate cancer correlates with faster metastasis and poorer survival, suggesting that restoring its levels could improve therapy sensitivity.