{"doi":"10.1101/2021.04.26.441477","title":"A pro-metastatic tRNA fragment drives Nucleolin oligomerization and stabilization of bound metabolic mRNAs","abstract":"SUMMARY Stress-induced cleavage of transfer RNAs (tRNAs) into tRNA-derived fragments (tRFs) occurs across organisms from yeast to human, yet its mechanistic bases and pathological consequences remain poorly defined. By performing genome-wide small RNA profiling, we detected increased abundance of a Cysteine tRNA fragment (5’-tRF Cys ) during breast cancer metastatic progression. 5’’-tRF Cys is required for efficient breast cancer metastatic lung colonization and metastatic cell survival. We identified Nucleolin as the direct binding partner of 5’-tRF Cys . 5’-tRF Cys binding enhanced the stability of Nucleolin’s associated pro-metastatic transcripts encoding metabolic enzymes Mthfd1l and Pafah1b1. 5’-tRF Cys stabilized these transcripts by promoting Nucleolin oligomerization and the assembly of Nucleolin and its bound transcripts into a higher-order ribonucleoprotein complex. Our findings reveal that a tRF can promote oligomerization of an RNA binding protein into a stabilizing ribonucleoprotein complex containing specific target transcripts, thereby driving specific metabolic pathways underlying cancer progression.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":220637,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9469,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":238458,"name":"Hanan Alwaseem","orcid":"0000-0002-4946-1436","position":1,"is_corresponding":false},{"id":106394,"name":"Henrik Molina","orcid":"0000-0001-8950-4990","position":2,"is_corresponding":false},{"id":258945,"name":"Bernardo Tavora","orcid":"0000-0003-4118-7505","position":3,"is_corresponding":false},{"id":258953,"name":"Sohail F. Tavazoie","orcid":"0000-0002-4966-9018","position":4,"is_corresponding":false},{"id":258950,"name":"Xuhang Liu","orcid":"0000-0002-7790-9701","position":0,"is_corresponding":true}],"reference_count":109,"raw_metadata":null,"created_at":"2026-07-18T23:53:46.965811Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}