{"doi":"10.1016/j.molcel.2025.08.034","title":"Matrin-3 forms spherical and wormlike assemblies that are modulated by RNA binding and ALS/FTD-associated mutations","abstract":"Matrin-3 (MATR3) is an RNA-binding protein (RBP) that is associated with familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). MATR3 features two RNA recognition motifs, two zinc-finger motifs, and four intrinsically disordered regions. Here, we report that human MATR3 associates with itself to form nanoscale spherical assemblies at ultralow protein concentrations. Through concentration-dependent associations, the spheres, which are 20-30 nm in diameter, transition into wormlike assemblies. These observations are reminiscent of sphere-to-worm transitions and micellization of amphiphilic molecules. Using computations and experiments, we discovered that the pattern of inter-domain attractions and repulsions gives MATR3 an inverse bolaamphiphile-like architecture that explains the concentration-dependent assembly characteristics. RNA binding causes shortening of wormlike assemblies of MATR3, whereas ALS/FTD-associated mutations render MATR3 assemblies less responsive to modulation by RNA. Overall, our findings highlight the unique assemblies formed by MATR3 while also showing how RNA-dependent interactions and ALS/FTD-associated mutations modulate the assemblies.","journal":"Molecular Cell","year":2025,"id":518713,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9626,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":418457,"name":"Min Kyung Shinn","orcid":"0000-0003-2713-5602","position":1,"is_corresponding":false},{"id":1387081,"name":"Sabrina K Talir","orcid":null,"position":2,"is_corresponding":false},{"id":888287,"name":"Ken Lee","orcid":"0000-0003-1971-8752","position":3,"is_corresponding":false},{"id":107331,"name":"Rohit V. Pappu","orcid":"0000-0003-2568-1378","position":4,"is_corresponding":false},{"id":444031,"name":"Meredith E. Jackrel","orcid":"0000-0003-4406-9504","position":5,"is_corresponding":false},{"id":677693,"name":"Macy L. Sprunger","orcid":null,"position":0,"is_corresponding":true}],"reference_count":127,"raw_metadata":null,"created_at":"2026-07-19T02:49:14.184995Z","pmid":"40975059","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":[]}