{"doi":"10.1083/jcb.202101019","title":"Translational regulation in the brain by TDP-43 phase separation","abstract":"The in vivo physiological function of liquid-liquid phase separation (LLPS) that governs non-membrane-bound structures remains elusive. Among LLPS-prone proteins, TAR DNA-binding protein of 43 kD (TDP-43) is under intense investigation because of its close association with neurological disorders. Here, we generated mice expressing endogenous LLPS-deficient murine TDP-43. LLPS-deficient TDP-43 mice demonstrate impaired neuronal function and behavioral abnormalities specifically related to brain function. Brain neurons of these mice, however, did not show TDP-43 proteinopathy or neurodegeneration. Instead, the global rate of protein synthesis was found to be greatly enhanced by TDP-43 LLPS loss. Mechanistically, TDP-43 LLPS ablation increased its association with PABPC4, RPS6, RPL7, and other translational factors. The physical interactions between TDP-43 and translational factors relies on a motif, the deletion of which abolished the impact of LLPS-deficient TDP-43 on translation. Our findings show a specific physiological role for TDP-43 LLPS in the regulation of brain function and uncover an intriguing novel molecular mechanism of translational control by LLPS.","journal":"The Journal of Cell Biology","year":2021,"id":159867,"datarank":1.1143257965430222,"base_score":3.6888794541139363,"endowment":3.6888794541139363,"self_citation_contribution":0.5533319181170905,"citation_network_contribution":0.5609938784259318,"self_endowment_contribution":0.5533319181170905,"citer_contribution":0.5609938784259318,"corpus_percentile":null,"corpus_rank":null,"citation_count":39,"citer_count":36,"citers_with_citation_signal":29,"citers_with_endowment":29,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9654,"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":276791,"name":"Luwen Wang","orcid":null,"position":1,"is_corresponding":false},{"id":671852,"name":"Xiaojia Ren","orcid":null,"position":2,"is_corresponding":false},{"id":671853,"name":"Justin Dunn","orcid":null,"position":3,"is_corresponding":false},{"id":671854,"name":"Ariele Peters","orcid":null,"position":4,"is_corresponding":false},{"id":361702,"name":"Masaru Miyagi","orcid":"0000-0003-4325-1216","position":5,"is_corresponding":false},{"id":247913,"name":"Hisashi Fujioka","orcid":"0000-0001-8511-7141","position":6,"is_corresponding":false},{"id":671370,"name":"Fangli Zhao","orcid":"0000-0003-3855-3885","position":7,"is_corresponding":false},{"id":671855,"name":"Candice C. Askwith","orcid":null,"position":8,"is_corresponding":false},{"id":479731,"name":"Jingjing Liang","orcid":"0000-0002-4623-9864","position":9,"is_corresponding":false},{"id":266957,"name":"Xinglong Wang","orcid":"0000-0001-8657-0159","position":10,"is_corresponding":false},{"id":479732,"name":"Ju Gao","orcid":"0000-0001-5893-9406","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:44:39.550981Z","pmid":"34427634","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":[]}