{"doi":"10.1101/2020.02.16.951954","title":"The tRNA pseudouridine synthase TruB1 regulates the maturation and function of let-7 miRNA","abstract":"Abstract Let-7 is an evolutionary conserved microRNA that mediates post-transcriptional gene silencing to regulate a wide range of biological processes, including development, differentiation, and tumor suppression. Let-7 biogenesis is tightly regulated by several RNA-binding proteins, including Lin28A/B, which represses let-7 maturation. To identify new regulators of let-7, we devised a cell-based functional screen of RNA-binding proteins using a let-7 sensor luciferase reporter, and identified the tRNA pseudouridine synthase, TruB1. TruB1 enhanced maturation specifically of let-7 family members. Rather than inducing pseudouridylation of the miRNAs, HITS-CLIP (High throughput sequencing crosslinking immunoprecipitation) and biochemical analyses revealed direct binding between endogenous TruB1 and the stem-loop structure of pri-let-7, which also binds Lin28A/B. TruB1 selectively enhanced the interaction between pri-let-7 and the microprocessor DGCR-8, which mediates miRNA maturation. Finally, TruB1 suppressed cell proliferation, which was mediated in part by let-7. Altogether, we reveal an unexpected function for TruB1 in promoting let-7 maturation and function.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":128944,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9632,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":323950,"name":"Tomoki Chiba","orcid":"0000-0001-5472-9030","position":1,"is_corresponding":false},{"id":323952,"name":"Yoshiaki Ito","orcid":"0000-0001-8564-2966","position":2,"is_corresponding":false},{"id":476786,"name":"Takahide Matsushima","orcid":"0000-0002-7110-2261","position":3,"is_corresponding":false},{"id":476787,"name":"Yuki Yano","orcid":"0000-0001-7706-1862","position":4,"is_corresponding":false},{"id":476788,"name":"Kohei Miyata","orcid":"0000-0003-0312-4810","position":5,"is_corresponding":false},{"id":236036,"name":"Tsutomu Suzuki","orcid":"0000-0002-9731-1731","position":6,"is_corresponding":false},{"id":476789,"name":"Kozo Tomita","orcid":"0000-0002-7374-3898","position":7,"is_corresponding":false},{"id":302983,"name":"Hiroshi Asahara","orcid":"0000-0002-5215-8745","position":8,"is_corresponding":false},{"id":323948,"name":"Ryota Kurimoto","orcid":"0000-0003-3029-5287","position":0,"is_corresponding":true}],"reference_count":90,"raw_metadata":null,"created_at":"2026-07-18T23:15:42.522809Z","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":[]}