{"doi":"10.1534/g3.120.401042","title":"<i>let-7-Complex</i> MicroRNAs Regulate Broad-Z3, Which Together with Chinmo Maintains Adult Lineage Neurons in an Immature State","abstract":"Abstract During Drosophila melanogaster metamorphosis, arrested immature neurons born during larval development differentiate into their functional adult form. This differentiation coincides with the downregulation of two zinc-finger transcription factors, Chronologically Inappropriate Morphogenesis (Chinmo) and the Z3 isoform of Broad (Br-Z3). Here, we show that br-Z3 is regulated by two microRNAs, let-7 and miR-125, that are activated at the larval-to-pupal transition and are known to also regulate chinmo. The br-Z3 3′UTR contains functional binding sites for both let-7 and miR-125 that confers sensitivity to both of these microRNAs, as determined by deletion analysis in reporter assays. Forced expression of let-7 and miR-125 miRNAs leads to early silencing of Br-Z3 and Chinmo and is associated with inappropriate neuronal sprouting and outgrowth. Similar phenotypes were observed by the combined but not separate depletion of br-Z3 and chinmo. Because persistent Br-Z3 was not detected in let-7-C mutants, this work suggests a model in which let-7 and miR-125 activation at the onset of metamorphosis may act as a failsafe mechanism that ensures the coordinated silencing of both br-Z3 and chinmo needed for the timely outgrowth of neurons arrested during larval development. The let-7 and miR-125 binding site sequences are conserved across Drosophila species and possibly other insects as well, suggesting that this functional relationship is evolutionarily conserved.","journal":"G3 Genes Genomes Genetics","year":2020,"id":74188,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9594,"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":388428,"name":"Geetanjali Chawla","orcid":"0000-0003-0354-3716","position":1,"is_corresponding":false},{"id":388429,"name":"Nicholas S. Sokol","orcid":"0000-0002-2768-4102","position":2,"is_corresponding":false},{"id":389521,"name":"Yen-Chi Wu","orcid":null,"position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-18T21:45:52.171053Z","pmid":"32071070","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":[]}