{"database":"biostudies-arrayexpress","file_versions":[],"scores":null,"additional":{"submitter":["Francesca Rapino"],"organism":["Mus musculus"],"software":["MiXCR v4.1.2"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/E-MTAB-13868"],"description":["The tRNA epitranscriptome is composed of a wide variety of base modifications in tRNAs and is emerging as a potential key vulnerability of cancer. Wobble tRNA modifications are required for specific codon decoding during translation and maintenance of protein homeostasis and support cancer metastasis and resistance to therapy. Here we show that ablation of enzymes catalyzing wobble uridine (U34) tRNA modification (U34 enzymes) remodels the MHC-II-associated antigen repertoire of melanoma by perturbing codon-specific mRNA translation. This perturbation in translation triggers the formation of aggregates that are subsequently degraded through the autophagy-lysosomal pathway and presented on MHC-II. The remodeled MHC-II repertoire in turn induces a CD4+ effector T cell-mediated anti-tumor response displaying specific clonal selection and immunodominance in melanoma. Our results identify a novel, potentially tractable, vulnerability of melanoma, in which codon-specific mRNA translation through wobble uridine tRNA modification, optimizes proteome homeostasis, prevents excessive antigen presentation, and limits T cell activity in melanoma."],"repository":["biostudies-arrayexpress"],"sample_protocol":["Library Construction - TCR beta and beta libraries preparation was performed using Mouse TCR RNA kit (Milaboratories) according to the manufacturer protocol (first PCR amplification - 21 cycles, second PCR - 14 cycles).","Nucleic Acid Extraction - RNA from CD4 T cells was extracted using Qiagen RNAeasy mini kit.","Sample Collection - Mouse CD4 T cells were sorted from melanoma samples","Sequencing - After 2nd PCR amplification the libraries were pooled, purified and sequenced on Miseq sequencer (Illumina) using 300 cycles v2 sequencing kit (library loading concentration - 12pM, 25% PhiX)."],"figure_sub":["Organization","MINSEQE Score","Assays and Data","Processed Data","MAGE-TAB Files"],"data_protocol":["Data Transformation - Demultiplexed fastq files were analyzed using MiXCR software (version 4.1.2)."],"omics_type":["Unknown","Transcriptomics","Genomics","Proteomics"],"instrument_platform":["Illumina MiSeq"],"study_type":["RNA-seq of total RNA"],"species":["Mus musculus"],"pubmed_authors":["Francesca Rapino","Alex Davydov","Pierre Close"],"additional_accession":[]},"is_claimable":false,"name":"TCR beta sequencing of CD4+ Tcells infiltrating melanoma B16 control or depleted of Elp3","description":"The tRNA epitranscriptome is composed of a wide variety of base modifications in tRNAs and is emerging as a potential key vulnerability of cancer. Wobble tRNA modifications are required for specific codon decoding during translation and maintenance of protein homeostasis and support cancer metastasis and resistance to therapy. Here we show that ablation of enzymes catalyzing wobble uridine (U34) tRNA modification (U34 enzymes) remodels the MHC-II-associated antigen repertoire of melanoma by perturbing codon-specific mRNA translation. This perturbation in translation triggers the formation of aggregates that are subsequently degraded through the autophagy-lysosomal pathway and presented on MHC-II. The remodeled MHC-II repertoire in turn induces a CD4+ effector T cell-mediated anti-tumor response displaying specific clonal selection and immunodominance in melanoma. Our results identify a novel, potentially tractable, vulnerability of melanoma, in which codon-specific mRNA translation through wobble uridine tRNA modification, optimizes proteome homeostasis, prevents excessive antigen presentation, and limits T cell activity in melanoma.","dates":{"release":"2026-02-27T00:00:00Z","modification":"2026-02-27T02:02:14.607Z","creation":"2024-02-28T19:49:46.799Z"},"accession":"E-MTAB-13868","cross_references":{"ENA":["ERP158226"],"EFO":["EFO_0002944","EFO_0004170","EFO_0009653","EFO_0005518","EFO_0003816","EFO_0004184"]}}