{"doi":"10.1016/j.molcel.2023.10.028","title":"FMRP phosphorylation modulates neuronal translation through YTHDF1","abstract":"RNA-binding proteins (RBPs) control messenger RNA fate in neurons. Here, we report a mechanism that the stimuli-induced neuronal translation is mediated by phosphorylation of a YTHDF1-binding protein FMRP. Mechanistically, YTHDF1 can condense with ribosomal proteins to promote the translation of its mRNA targets. FMRP regulates this process by sequestering YTHDF1 away from the ribosome; upon neuronal stimulation, FMRP becomes phosphorylated and releases YTHDF1 for translation upregulation. We show that a new small molecule inhibitor of YTHDF1 can reverse fragile X syndrome (FXS) developmental defects associated with FMRP deficiency in an organoid model. Our study thus reveals that FMRP and its phosphorylation are important regulators of activity-dependent translation during neuronal development and stimulation and identifies YTHDF1 as a potential therapeutic target for FXS in which developmental defects caused by FMRP depletion could be reversed through YTHDF1 inhibition.","journal":"Molecular Cell","year":2023,"id":317087,"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":85,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9583,"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":243016,"name":"Jiangbo Wei","orcid":"0000-0003-2691-6490","position":1,"is_corresponding":false},{"id":986718,"name":"Yantao Chen","orcid":"0000-0001-5364-8263","position":2,"is_corresponding":false},{"id":620457,"name":"Yunhee Kang","orcid":"0000-0001-5622-4570","position":3,"is_corresponding":false},{"id":87792,"name":"Hailing Shi","orcid":"0000-0001-7355-378X","position":4,"is_corresponding":false},{"id":1021683,"name":"Fan Yang","orcid":"0000-0001-5873-4662","position":5,"is_corresponding":false},{"id":1021684,"name":"Zhuoyue Shi","orcid":"0009-0005-0765-0545","position":6,"is_corresponding":false},{"id":986719,"name":"Shijie Chen","orcid":"0000-0001-9724-7453","position":7,"is_corresponding":false},{"id":383894,"name":"Ying Zhou","orcid":"0000-0003-3607-8216","position":8,"is_corresponding":false},{"id":474682,"name":"Caraline Sepich‐Poore","orcid":"0000-0002-1853-4647","position":9,"is_corresponding":false},{"id":563793,"name":"Xiaoxi Zhuang","orcid":"0000-0001-6825-3221","position":10,"is_corresponding":false},{"id":342863,"name":"Xiaoming Zhou","orcid":"0000-0002-6840-973X","position":11,"is_corresponding":false},{"id":749831,"name":"Hualiang Jiang","orcid":"0000-0003-0656-6315","position":12,"is_corresponding":false},{"id":227213,"name":"Zhexing Wen","orcid":"0000-0002-1518-3845","position":13,"is_corresponding":false},{"id":307991,"name":"Peng Jin","orcid":"0000-0001-6137-6659","position":14,"is_corresponding":false},{"id":114863,"name":"Cheng Luo","orcid":"0000-0003-3864-8382","position":15,"is_corresponding":false},{"id":21408,"name":"Chuan He","orcid":"0000-0003-4319-7424","position":16,"is_corresponding":false},{"id":274848,"name":"Zhongyu Zou","orcid":"0000-0001-7152-5435","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T01:06:44.698773Z","pmid":"37949069","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":[]}