{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE336nnn/GSE336632/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE336632"],"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 [CUT&Run]","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":"GSE336632","cross_references":{"GSM":["GSM9839071","GSM9839060","GSM9839061","GSM9839072","GSM9839050","GSM9839051","GSM9839073","GSM9839063","GSM9839052","GSM9839070","GSM9839068","GSM9839057","GSM9839058","GSM9839069","GSM9839075","GSM9839053","GSM9839064","GSM9839065","GSM9839054","GSM9839066","GSM9839077","GSM9839055","GSM9839056","GSM9839067"],"GPL":["24676"],"GSE":["336632"],"taxon":["Homo sapiens"]}}