{"doi":"10.7554/elife.89903.1.sa1","title":"Reviewer #1 (Public Review): Essential Function of Membrane-Bound Transcription Factor MYRF in Promoting Transcription of miRNA lin-4 during C. elegans Development","abstract":"Precise developmental timing control is essential for organism formation and function, but its mechanisms are unclear. In C. elegans, the microRNA lin-4 plays a critical role in developmental timing. While lin-4’s downregulation of LIN-14 is well-established, the mechanisms behind lin-4 upregulation remain unknown. We demonstrate that the membrane-associated transcription factor MYRF-1 is necessary for lin-4 upregulation in late L1 stage. MYRF-1 is initially localized on the cell membrane, and its increased cleavage and nuclear accumulation coincide with lin-4 expression timing. We show that MYRF-1 regulates lin-4 expression cell-autonomously and that hyperactive MYRF-1 can prematurely drive lin-4 expression in early L1 and embryos. The tandem lin-4 promoter DNA recruits MYRF-1GFP to form visible loci in the nucleus, suggesting that MYRF-1 directly acts on the lin-4 promoter. Our findings identify a crucial link in understanding developmental timing regulation and establish MYRF-1 as a key regulator of lin-4 expression.","journal":null,"year":2023,"id":410172,"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":0.9515,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":132484,"name":"Wang Zhao","orcid":"0000-0003-0848-5738","position":1,"is_corresponding":false},{"id":108747,"name":"Lifang Wang","orcid":"0000-0001-8950-4069","position":2,"is_corresponding":false},{"id":1189922,"name":"Benling Qi","orcid":"0000-0003-3149-5707","position":3,"is_corresponding":false},{"id":1190303,"name":"Xu Zhimin","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T01:21:31.144858Z","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":[]}