GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE336nnn/GSE336635/primary200OKTranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE336635GEOGSEfalsetRNA dosage regulates lineage plasticity and therapy resistance in prostate cancer through codon bias [RNA-seq]Lineage plasticity underlies therapeutic resistance in cancer, yet the translational mechanisms enabling this phenotypic flexibility remain largely unknown. Using prostate cancer as a paradigm of lineage dependence, we performed unbiased small RNA sequencing and identified tRNAArg(UCU)-1 as a regulator of lineage transitions and therapy resistance. tRNAArg(UCU)-1 is both necessary and sufficient to reprogram lineage dependence which can be tuned to restore sensitivity to androgen receptor-targeted therapies. We identify TARDBP and ZSCAN29 as DNA-binding proteins that directly engage the genomic locus of tRNAArg(UCU)-1 to regulate its expression revealing the importance of non-canonical tRNA-specific gene regulation. Mechanistically, tRNAArg(UCU)-1 controls a translational program centered on SWI/SNF chromatin remodelers, which are necessary to maintain lineage fidelity. In patients, tRNAArg(UCU)-1 is downregulated in neuroendocrine prostate cancer and its loss is associated with accelerated metastasis and poor survival. These findings uncover a previously unrecognized tRNA-specific regulatory axis that links codon biology to lineage dependence and therapy resistance in prostate cancer.2026/08/26GSE336635GSM9839140GSM9839145GSM9839146GSM9839147GSM9839148GSM9839141GSM9839149GSM9839150GSM9839151GSM9839156GSM9839113GSM9839157GSM9839158GSM9839114GSM9839115GSM9839159GSM9839152GSM9839153GSM9839154GSM9839155GSM9839116GSM9839117GSM9839118GSM9839119GSM9839160GSM9839161GSM9839162GSM9839123GSM9839167GSM9839124GSM9839125GSM9839126GSM9839163GSM9839120GSM9839164GSM9839121GSM9839165GSM9839166GSM9839122GSM9839127GSM9839128GSM9839129GSM9839134GSM9839135GSM9839136GSM9839137GSM9839130GSM9839131GSM9839132GSM9839133GSM9839138GSM983913924676336635Homo sapiens