{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301566/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301566"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"tRNA dosage regulates lineage plasticity and therapy resistance in prostate cancer through codon bias [Polysome-seq]","description":"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.","dates":{"publication":"2026/08/26"},"accession":"GSE301566","cross_references":{"GSM":["GSM9085425","GSM9085403","GSM9085404","GSM9085426","GSM9085401","GSM9085424","GSM9085402","GSM9085407","GSM9085429","GSM9085427","GSM9085405","GSM9085428","GSM9085406","GSM9085391","GSM9085392","GSM9085390","GSM9085395","GSM9085396","GSM9085393","GSM9085394","GSM9085399","GSM9085432","GSM9085433","GSM9085430","GSM9085397","GSM9085431","GSM9085398","GSM9085436","GSM9085437","GSM9085434","GSM9085435","GSM9085438","GSM9085439","GSM9085384","GSM9085385","GSM9085388","GSM9085400","GSM9085389","GSM9085386","GSM9085387"],"GPL":["24676"],"GSE":["301566"],"taxon":["Homo sapiens"]}}