{"doi":"10.1016/j.celrep.2024.113999","title":"Depletion of Mettl3 in cholinergic neurons causes adult-onset neuromuscular degeneration","abstract":"Motor neuron (MN) demise is a hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Post-transcriptional gene regulation can control RNA's fate, and defects in RNA processing are critical determinants of MN degeneration. N 6 -methyladenosine (m 6 A) is a post-transcriptional RNA modification that controls diverse aspects of RNA metabolism. To assess the m 6 A requirement in MNs, we depleted the m 6 A methyltransferase-like 3 (METTL3) in cells and mice. METTL3 depletion in embryonic stem cell-derived MNs has profound and selective effects on survival and neurite outgrowth. Mice with cholinergic neuron-specific METTL3 depletion display a progressive decline in motor behavior, accompanied by MN loss and muscle denervation, culminating in paralysis and death. Reader proteins convey m 6 A effects, and their silencing phenocopies METTL3 depletion. Among the m 6 A targets, we identified transactive response DNA-binding protein 43 (TDP-43) and discovered that its expression is under epitranscriptomic control. Thus, impaired m 6 A signaling disrupts MN homeostasis and triggers neurodegeneration conceivably through TDP-43 deregulation.","journal":"Cell Reports","year":2024,"id":438118,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1247957,"name":"Mattia Furlan","orcid":"0000-0002-5460-6660","position":1,"is_corresponding":false},{"id":1247958,"name":"Iris Tanaka","orcid":"0000-0003-0185-0034","position":2,"is_corresponding":false},{"id":832027,"name":"Tommaso Leonardi","orcid":"0000-0002-4449-1863","position":3,"is_corresponding":false},{"id":343926,"name":"Paola Rinchetti","orcid":"0000-0001-8279-3304","position":4,"is_corresponding":false},{"id":1248364,"name":"Patricia M.S. Passos","orcid":null,"position":5,"is_corresponding":false},{"id":1248365,"name":"Alliny Bastos","orcid":null,"position":6,"is_corresponding":false},{"id":301613,"name":"Yuna M. Ayala","orcid":"0000-0003-4688-6583","position":7,"is_corresponding":false},{"id":28756,"name":"Jacob H. Hanna","orcid":"0000-0003-2042-9974","position":8,"is_corresponding":false},{"id":347873,"name":"Serge Przedborski","orcid":"0000-0002-7283-3883","position":9,"is_corresponding":false},{"id":696566,"name":"Dario Bonanomi","orcid":"0000-0003-4517-1244","position":10,"is_corresponding":false},{"id":3783,"name":"Mattia Pelizzola","orcid":"0000-0001-6672-9636","position":11,"is_corresponding":false},{"id":343929,"name":"Francesco Lotti","orcid":"0000-0002-5104-9088","position":12,"is_corresponding":false},{"id":475886,"name":"Georgia Dermentzaki","orcid":null,"position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":null,"created_at":"2026-07-19T02:00:38.888629Z","pmid":"38554281","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":[]}